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51,560 Abstracts & Growing Daily. Sourced from the US National Library of Medicine.

601
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Pterostilbene may elicit an oral anticancer response in drug-resistant cells.


Pterostilbene is a natural polyphenolic compound that is primarily found in fruits, such as blueberries and has a similar structure to resveratrol. Pterostilbene exhibits antioxidant, anti-inflammatory and antitumor activity but the effects of pterostilbene on drug-resistant oral cancer cells and its underlying mechanisms of action have not yet been explored. Therefore, the present study was performed to clarify the anticancer effects of pterostilbene on cisplatin-resistant human oral cancer CAR cells. The results demonstrated that CAR cells exhibited marked shrinkage, cell membrane breakage and autophagic vacuole formation following treatment with pterostilbene. Pterostilbene also effectively inhibited cell viability and suppressed cell confluence in a time- and concentration-dependent manner. Probing with acridine orange, monodansylcadaverine and LysoTracker Red demonstrated that the number of acidic vesicular organelles was increased, indicating increased autophagy. Furthermore, Heochst 33342 staining determined that DNA condensation, a characteristic of apoptosis, was enhanced following treatment with pterostilbene. Furthermore, pterostilbene upregulated mRNA levels of LC3-II and Atg12, as well as the expression of Atgs/Beclin-1/LC3-associated signaling, suggesting that it enhances autophagy. The autophagy inhibitors 3-methyladenine and chloroquine were used to confirm that pterostilbene induces autophagy. It was also determined that pterostilbene triggered caspase-dependent apoptosis by directly testing DNA breakage and using the pan-caspase inhibitor carbobenzoxyvalyl-alanyl-aspartyl fluoromethyl ketone. The results demonstrated that pterostilbene mediates the apoptosis of CAR cells via the intrinsic apoptotic cascade. In addition, pterostilbene inhibited MDR1 expression and the phosphorylation of AKT on the Ser473 site in CAR cells. Therefore, pterostilbene may elicit an oral anticancer response in drug-resistant cells and may be used as a chemotherapeutic adjuvant to treat patients with oral cancer.

Int J Oncol. 2018 Mar 2. Epub 2018 Mar 2. PMID: 29512708

602
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Resveratrol and pterostilbene exhibit anticancer properties involving the downregulation of HPV oncoprotein E6 in cervical cancer cells.


Cervical cancer is one of the most common cancers in women living in developing countries. Due to a lack of affordable effective therapy, research into alternative anticancer compounds with low toxicity such as dietary polyphenols has continued. Our aim is to determine whether two structurally similar plant polyphenols, resveratrol and pterostilbene, exhibit anticancer and anti-HPV (Human papillomavirus) activity against cervical cancer cells. To determine anticancer activity, extensive in vitro analyses were performed. Anti-HPV activity, through measuring E6 protein levels, subsequent downstream p53 effects, and caspase-3 activation, were studied to understand a possible mechanism of action. Both polyphenols are effective agents in targeting cervical cancer cells, having low IC50 values in theµM range. They decrease clonogenic survival, reduce cell migration, arrest cells at the S-phase, and reduce the number of mitotic cells. These findings were significant, with pterostilbene often being more effective than resveratrol. Resveratrol and to a greater extent pterostilbene downregulates the HPV oncoprotein E6, induces caspase-3 activation, and upregulates p53 protein levels. Results point to a mechanism that may involve the downregulation of the HPV E6 oncoprotein, activation of apoptotic pathways, and re-establishment of functional p53 protein, with pterostilbene showing greater efficacy than resveratrol.

Nutrients. 2018 Feb 21 ;10(2). Epub 2018 Feb 21. PMID: 29485619

603
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The use of curcumin may be a promising therapeutic approach to the treatment of patients with pancreatic cancer.


Curcumin is a natural polyphenol compound derived from turmeric. It possesses multiple pharmacological properties, including antioxidant, anti-inflammatory and anti-tumor progression properties. Our recent study demonstrated that superoxide dismutase (SOD)-dependent production of hydrogen peroxide (H2O2) promoted the invasive and migratory activity of pancreatic cancer cells. However, whether curcumin suppresses SOD-induced cancer progression and the related mechanisms remains unclear. Since epithelial‑to-mesenchymal transition (EMT) plays a key role in tumor metastasis, the aim of the present study was to examine whether curcumin intervenes with SOD-induced EMT in pancreatic cancer and the underlying mechanism. The human pancreaticcancer cells BxPC-3 and Panc-1 were exposed to SOD in the presence or absence of curcumin, catalase (CAT, a scavenger of H2O2), or LY 294002 [a phosphoinositide-3 kinase (PI3K) inhibitor]. Intracellular reactive oxygen species (ROS) and H2O2 were evaluated by 2,7-dichlorodihydrofluorecein diacetate and H2O2 assay, respectively. The activation of p-Akt and p-nuclear factor (NF)-κB were examined by western blotting. The migratory and invasive abilities of pancreatic cancer cells were tested by the wound healing and Transwell invasion assays. The expression of E-cadherin, N-cadherin and vimentin (EMT-related genes) were measured by reverse transcription-quantitative polymerase chain reaction and western blotting at the mRNA and protein levels, respectively. The findings of the present study demonstrated that curcumin decreased SOD-induced production of ROS and H2O2 in BxPC-3 and Panc-1cells. Curcumin was able to suppress SOD-induced invasion and migration, and it also regulated the expression of the above‑mentioned EMT-related genes and cell morphology. SOD-induced cell invasion was also inhibited by catalase and LY 294002. Furthermore, the levels of p-Akt and p-NF-κB caused by SOD could be offset by treatment with curcumin and LY 294002. To summarize, these results demonstrated that curcumin was able to prevent SOD-driven H2O2-induced pancreatic cancer metastasis by blocking the PI3K/Akt/NF-κB signaling pathway. The use of curcumin to inhibit the H2O2/Akt/NF-κB axis may be a promising therapeutic approach to the treatment of patients with pancreatic cancer.

Int J Oncol. 2018 Mar 1. Epub 2018 Mar 1. PMID: 29512729

604
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Curcumin potentiates the potent antitumor activity of ACNU against glioblastoma.


Glioblastoma (GBM) is a highly invasive and challenging primary tumor of the central nervous system (CNS), and currently available treatments provide limited benefits to patients with this disease. Therefore, the development of novel therapeutic targets and effective treatment strategies is essential. Nimustine hydrochloride (ACNU) is widely used as the standard chemotherapeutic agent and is frequently administered together with other chemotherapeutic agents in clinical studies. Curcumin, a natural polyphenolic compound, could potentially be combined with chemotherapeutics for cancer treatment; however, there are no reports of studies where ACNU and curcumin were combined for GBM treatment, and the mechanisms underlying their activity remain poorly understood. In the present study, we investigated the effects of combined treatment with curcumin and ACNU on GBM cells and found that it significantly enhanced the inhibition of cell proliferation, colony formation, migration, and invasion. In addition, co-treatment with curcumin increased ACNU-induced apoptosis through enhancing the release of cytochrome c from the mitochondrial intermembrane space into the cytosol. Further, curcumin and ACNU acted synergistically in their antitumor effects by targeting N-cadherin/MMP2/9, PI3K/AKT, and NF-κB/COX-2 signaling. These results indicate that curcumin can enhance the anti-proliferation, anti-migration, and proapoptotic activities of ACNU against GBM, and provide strong evidence that combined treatment with curcumin and ACNU has the potential to be an effective therapeutic option for GBM.

Onco Targets Ther. 2017 ;10:5471-5482. Epub 2017 Nov 15. PMID: 29180881

605
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Curcumin is a natural pan-histone deacetylase inhibitor in cancer.


BACKGROUND: Histone deacetylases (HDACs) are a group of histone modification enzymes with pivotal role in disease pathogenesis especially in cancer development. Increased activity of certain types of HDACs and positive effects of HDAC inhibition has been shown in several types of cancers. Furthermore, few HDAC inhibitors have been approved by the FDA for cancer treatment, and this has generated interest in finding new HDAC inhibitors as potential anti-cancer agents. Curcumin, a natural polyphenol extracted from turmeric, is a safe and bioactive phytochemical with a wide range of molecular targets and pharmacological activities including promising anti-cancer properties.METHODS: A systematic literature search using appropriate keywords was made to identify articles reporting the modulatory effect of curcumin on HDACs in different types of cancer in vitro and in vivo.RESULTS: HDACs have emerged as novel targets of curcumin that their modulation may contribute to the putative anti-cancer effects of curcumin. Curcumin inhibits HDAC activity, and down-regulates the expression of HDAC types 1, 2, 3, 4, 5, 6, 8 and 11 in different cancer cell lines and mice, while the activity and expression of HDAC2 have been reported to be up-regulated by curcumin in COPD and heart failure models.CONCLUSION: Available in vitro and in vivo data are encouraging and in favor of the HDAC inhibitory activity of curcumin but clinical evidence on the efficacy of curcumin as an adjunct treatment in cancer patients is lacking.

Curr Pharm Des. 2017 Nov 14. Epub 2017 Nov 14. PMID: 29141538

606
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Naturally occurring immunomodulators with antitumor activity.


Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities. The anticancer activity of these immunomodulators is due to their anti-inflammatory, antioxidant, and induction of apoptosis, anti-angiogenesis, and anti-metastasis effect. These natural immunomodulators such as genistein, curcumin, and resveratrol can be used as prophylaxis against the initiation of cancer besides the inhibition of tumor growth and proliferation. Whereas, immunostimulants can elicit and activate humoral and cell-mediated immune responses against the tumor that facilitate the recognition and destruction of the already existing tumor. This review represents the recent studies on various natural immunomodulators with antitumor effects. We have focused on the relationship between their anticancer activity and immunomodulatory mechanisms. The mechanisms of action of various immunomodulators such as polyphenolic compounds, flavonoids, organosulfur compounds, capsaicin, vinca alkaloids, bromelain, betulinic acid and zerumbone, the affected cancerous cell lines in addition to the targeted molecules and transcriptional pathways have been review and critically analyzed.

Int Immunopharmacol. 2017 Sep ;50:291-304. PMID: 28734166

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This review highlights pomegranates role in prevention and treatment of breast, prostate, lung, colon, skin and hepatocellular cell cancers.


Cancer has become one of the most fatal diseases in most countries. In spite of the medical care developing, cancer still remains a significant problem. The majority of the cancers are resistant to treatment. Thus, the research for novel, more efficient and less side effect treatment methods continues. Pomegranate contains strong antioxidant activity, with potential health interests. Research concern in pomegranate is increasing because of their anticancer potential due to possess rich in polyphenols. We highlight the pomegranate potential health benefits and mechanism of cancer progression inhibition. Pomegranate has indicated antiproliferative, anti-metastatic and anti-invasive effects on different cancer cell line,and clinical trial. The aim of this review is to evaluate functional properties and the medical benifits of pomegranate against various cancer diseases. In addition, pomegranate properties inandexperimental human and animal clinical trials and its future use are explored. The available data suggest that(pomegranate) might be used in the control and potential therapeutic for some disease conditions and benefits human health status. This review summarizes,and clinical trial studies highlighting the pomegranate role in prevent and treatment of breast, prostate, lung, colon, skin and hepatocellular cell cancers.

Oncol Rev. 2018 Jan 30 ;12(1):345. Epub 2018 Jan 30. PMID: 29441150

608
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Antioxidant and hemolysis protective effects of polyphenol-rich extract from Mulberry fruits.


Background: Mulberry fruits are a superior source of polyphenol, especially anthocyanins that contribute potentially to the beneficial effects which include reducing the risk of cardiovascular diseases and cancers with antioxidant, anti-inflammatory, and chemoprotective properties.Objectives: In this study, purification of the polyphenol-rich extract from mulberry fruit (MPE) was purified and assessed the activities of antioxidant and hemolysis protectiveand.Materials and Methods: Antioxidant activitieswas measured by quantifying its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, reducing power and Fe-chelating ability. MPE was purified by high-pressure liquid chromatography (HPLC) and analyzed individual polyphenols using liquid chromatography-mass spectrometry (LC-MS)/MS.Results: The total polyphenol content was 147.69± 0.02 mg gallic acid equivalents (GAE)/g dried weight (DW) in the extract and 403.55 ± 0.02 mg GAE/g DW in the purified extract. Further identification by HPLC-ultraviolet-visible and LC-MS/MS analysis indicated in MPE, an anthocyanin compound, cyanidin-3--glucoside. With regard toassays, MPE possessed antioxidant effect, especially in Fechelating ability with an ICvalue of 1.016 mg/mL. The protective effects on mouse red blood cell hemolysis and lipid peroxidationwere dose and time dependent.Conclusion: It indicates that MPE could be a good candidate for future biomedical applications to promote human health with limited side effects.SUMMARY: Mulberry fruit is an excellent source of polyphenols, in particular, anthocyanins, which has infinite health benefits. This study determined the predominant anthocyanin, cyanidin-3-glucoside, could possibly be the rationale behind the antioxidant and antihemolytic effect of MPE. Results indicate that MPE could be a good candidate for future biomedical applications to promote human health with limited side effects.MPE: Purification of the polyphenol-rich extract from mulberry fruit, LC-MS: Liquid chromatography-mass spectrometry, HPLC: High-pressure liquid chromatography, DPPH: 2,2-diphenyl-1-picrylhydrazyl scavenging activity, RBC: Red blood cell, GAE: Gallic acid equivalent, FeCl: Ferrous chloride, HO: Hydrogen peroxide, EDTA-2Na: Ethylenediaminetetraacetic acid disodium salt, PBS: Phosphate-buffered saline, TCA: Trichloroacetic acid, TBA: 2-thiobarbituric acid, FeSO: Ferrous sulphate, MDA: Malondialdehyde, V: Vitamin C, DW: Dried weight.

Pharmacogn Mag. 2018 Jan-Mar;14(53):103-109. Epub 2018 Feb 20. PMID: 29576709

609
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The consumption of tree nuts has been scientifically proven to improve lifespan and healthspan and should be a part of a healthy diet in the elderly.


Tree nuts, complete functional foods, contain macro- and micronutrients of high biological value. These bioactive compounds have a synergistic effect in preventing and delaying many age-related pathologies (e.g. cardiovascular diseases, stroke, type 2 diabetes mellitus, certain types of cancer, and several neurodegenerative diseases). Tree nuts are low in carbohydrates, but they abound in healthy fatty acids, in optimal proportion for a good plasma lipid profile, and are a good source of proteins, rich in proteinogenic amino acids. They contain significant amounts of vitamin E, minerals, polyphenols, and phytosterols. Polyphenols, which are powerful phytochemicals, act as direct and indirect antioxidants, reduce the inflammatory response, improve proteostasis and mitochondrial biogenesis, modulate many cell signaling pathways, have a major role in cytoprotection, are Nrf2/ARE activators, down-regulate the NFκB system, promote anticancer potential, and prevent cell senescence. Some of them have senolytic effects, interfere in specific cell signaling pathways modulated by caloric restriction, and protect against UV radiation and photoaging. Moreover, tree nuts are good prebiotics and improve gut microbiota. The stability of polyphenolic compounds and their antioxidant activity can be influenced by cooking techniques, temperature of storage, and post-harvest processing methods. The consumption of tree nuts has been scientifically proven to improve lifespan and healthspan and should be a part of a healthy diet in the elderly.

Food Funct. 2018 Apr 4. Epub 2018 Apr 4. PMID: 29616249

610
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Antioxidant and cancer chemopreventive activities of cistus and pomegranate polyphenols.


Polyphenol rich extracts obtained from cistus herb (Cistus incanus L.) and pomegranate peel (Punica granatum L.) exhibited significant antioxidant activity in V79 cell culture (Chinese hamster lung fibroblasts) -cistus extract reduced intracellular content of reactive oxygen species (ROS) by 30-40% and pomegranate extract by 29-36%. In human breast (MCF-7) and colon (LOVO) cancer cell lines cistus and pomegranate extracts decreased cancer cell growth both in drug-sensitive cells by 15-30% and in drug resistant (doxorubicin-resistant; DX) sublines by 5-20%. However, the extracts did not influence on cell growth%f normal hamster fibroblast cultures (V79). The extracts induced apoptosis in the tested cancer cell lines. Significantly higher proapoptotic impact of the extracts was observed in drug-sensitive than in drug-resistant sublines. The results suggest potential usefulness of the tested polyphenol rich extracts in people exposed to oxidative stress. Their potential use as adjuvant therapy of human cancers needs further studies.

Acta Pol Pharm. 2017 Mar ;74(2):688-698. PMID: 29624275

611
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These results suggest that dietary consumption of urolithin A could induce autophagy and inhibit human colorectal cancer cell metastasis.


Autophagy is an evolutionarily conserved pathway in which cytoplasmic contents are degraded and recycled. This study found that submicromolar concentrations of urolithin A, a major polyphenol metabolite, induced autophagy in SW620 colorectal cancer (CRC) cells. Exposure to urolithin A also dose-dependently decreased cell proliferation, delayed cell migration, and decreased matrix metalloproteinas-9 (MMP-9) activity. In addition, inhibition of autophagy by Atg5-siRNA, caspases by Z-VAD-FMK suppressed urolithin A-stimulated cell death and anti-metastatic effects. Micromolar urolithin A concentrations induced both autophagy and apoptosis. Urolithin A suppressed cell cycle progression and inhibited DNA synthesis. These results suggest that dietary consumption of urolithin A could induce autophagy and inhibit human CRC cell metastasis. Urolithins may thus contribute to CRC treatment and offer an alternative or adjunct chemotherapeutic agent to combat this disease.

Mol Carcinog. 2018 Feb ;57(2):193-200. Epub 2017 Nov 26. PMID: 28976622

612
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A review on phytochemistry and therapeutic uses of Hibiscus sabdariffa L.


Hibiscus sabdariffa L. (roselle) belonging to the Malvaceae family is widely grown in many countries. This plant is often used in the traditional medicine being rich in phytochemicals like polyphenols especially anthocyanins, polysaccharides and organic acids thus having enormous prospective in modern therapeutic uses. The study aimed to review and document all the available evidence and information about the calyces of Hibiscus sabdariffa (roselle) with the special focus on their nutritional composition, bioactive constituents and therapeutic uses. The electronic database was searched up to 2017, using keywords Hibiscus sabdariffa, chemical constituents of roselle, therapeutic uses of roselle. Journals, books and conference proceedings were also searched. The review provides valuable information about the nutraceutical component of Hibiscus sabdariffa L. and their utilization for curing various degenerative diseases like hypertension, hyperlipidemia, cancer and other inflammatory diseases of liver and kidney. Their toxicological effects have also been discussed from a safety point of view. Most studies supported and provided the scientific basis for the statement that Hibiscus sabdariffa and their active constituents play an important role in the prevention of chronic and degenerative diseases that are associated with oxidative stress. Our study suggests, that good research is needed, to establish a potential strategy that can balance the pharmacological and toxic effects of roselle and standardized fingerprint of Hibiscus sabdariffa is required internationally for quality control.

Biomed Pharmacother. 2018 Mar 26 ;102:575-586. Epub 2018 Mar 26. PMID: 29597091

613
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Phytochemical profiles and antioxidant activity of adlay varieties.


Consumption of whole grains has been associated with reduced risk of developing major chronic diseases. These health benefits have been attributed in part to their unique phytochemicals. Little is known about the complete profiles of phytochemicals and antioxidant activities of different adlay varieties. The objectives of this study were to determine the phytochemicals profiles of the three adlay varieties, including both free and bound of total phenolics and total flavonoids, and to determine the total antioxidant activity of adlay. The free, bound, and total phenolic contents of adlay samples ranged from 31.23 to 45.19 mg of gallic acid equiv/100 g of sample, from 28.07 to 30.86 mg of gallic acid equiv/100 g of sample, and from 59.30 to 76.04 mg of gallic acid equiv/100 g of sample, respectively. On average, the bound phenolics contributed 45.3% of total phenolic content of the adlay varieties analyzed. The free, bound, and total flavonoid contents of adlay samples ranged from 6.21 to 18.24 mg of catechin equiv/100 g, from 18.68 to 35.27 mg of catechin equiv/100 g, and from 24.88 to 52.86 mg of catechin equiv/100 g, respectively. The average values of bound flavonoids contributed 71.1% of total flavonoids of the adlay varieties analyzed. The percentage contribution of flavonoid content to phenolic content of free, bound, and total ranged from 11.6 to 35.2%, from 50.5 to 66.8%, and from 24.6 to 50.5%. The free, bound, and total oxygen radical absorbance capacity (ORAC) values of adlay samples ranged from 231.9 to 316.6 mg of Trolox equiv/100 g, from 209.0 to 351.4 mg of Trolox equiv/100 g, and from 440.9 to 668.0 mg of Trolox equiv/100 g, respectively. The average ORAC values of bound phytochemicals contributed 48.1% of total antioxidant activity of the adlay varieties analyzed. The content of total polyphenol and the antioxidant capacity are obviously different among different species. Liaoning 5 adlay and Longyi 1 adlay are significantly better than Guizhou heigu adlay. The adlay extracts have obvious proliferate inhibition on human liver cancer cells, and substantially in the experimental concentration range, the adlay sample itself has no cytotoxicity. Knowing the phytochemical profiles and antioxidant activity of adlay gives insights to its potential application to promote health.

J Agric Food Chem. 2013 May 29 ;61(21):5103-13. Epub 2013 May 16. PMID: 23647066

614
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Curcumin induces ROS independent apoptosis and cell cycle arrest in colon cancer cells that carry mutation on Smad4 and p53.


Curcumin is a natural dietary polyphenol compound that has various pharmacological activities such as antiproliferative and cancer-preventive activities on tumor cells. Indeed, the role reactive oxygen species (ROS) generated by curcumin on cell death and cell proliferation inhibition in colon cancer is poorly understood. In the present study, we hypothesized that curcumin-induced ROS may promote apoptosis and cell cycle arrest in colon cancer. To test this hypothesis, the apoptosis-inducing potential and cell cycle inhibition effect of ROS induced by curcumin was investigated in Smd4 and p53 mutated HT-29 colon adenocarcinoma cells. We found that curcumin treatment significantly increased the level of ROS in HT-29 cells in a dose- and time-dependent manner. Furthermore, curcumin treatment markedly decreased the cell viability and proliferation potential of HT-29 cells in a dose- and time-dependent manner. Conversely, generation of ROS and inhibitory effect of curcumin on HT-29 cells were abrogated by N-acetylcysteine treatment. In addition, curcumin treatment did not show any cytotoxic effects on HT-29 cells. Furthermore, curcumin-induced ROS generation caused the DNA fragmentation, chromatin condensation, and cell nuclear shrinkage and significantly increased apoptotic cells in a dose- and time-dependent manner in HT-29 cells. However, pretreatment of N-acetylcysteine inhibited the apoptosis-triggering effect of curcumin-induced ROS in HT-29 cells. In addition, curcumin-induced ROS effectively mediated cell cycle inhibition in HT-29 cells. In conclusion, our data provide the first evidence that curcumin induces ROS independent apoptosis and cell cycle arrest in colon cancer cells that carry mutation on Smad4 and p53.

Nutr Res. 2018 Mar ;51:67-81. Epub 2018 Jan 6. PMID: 29673545

615
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Cirsium japonicum extract and its active component cirsimaritin is an excellent candidate as an alternative anti-breast cancer treatment.


The biological activities of the ethanol extract from Cirsium japonicum var. maackii (ICF-1) and its major component, polyphenol cirsimaritin, were investigated as part of the search for possible alternative drugs for breast cancer. Three in vitro cell-based assays were used: the cell proliferation assay, tube-formation assay, and Western blot analysis. Both the ICF-1 extract and cirsimaritin inhibited the viability of HUVECs in a dose-dependent manner. The inhibition achieved was 36.89% at a level of 200μg/ml by the ICF-1 extract and 62.04% at a level of 100μM by cirsimaritin. The ICF-1 extract and cirsimaritin reduced tube formation by 12.69% at level of 25μg/ml and 32.18% at the levels of 6.25μM, respectively. Cirsimaritin inhibited angiogenesis by downregulation of VEGF, p-Akt and p-ERK in MDA-MB-231 cells, suggesting that cirsimaritin is potentially useful as an anti-metastatic agent. The present study demonstrated that Cirsium japonicum extract and its active component cirsimaritin is an excellent candidate as an alternative anti-breast cancer drug.

Bioorg Med Chem Lett. 2017 09 1 ;27(17):3968-3973. Epub 2017 Jul 29. PMID: 28784292

616
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Beneficial phytochemicals with anti-tumor potential revealed through metabolic profiling of new red pigmented lettuces.


The present study aimed to compare polyphenols among red lettuce cultivars and identify suitable cultivars for the development and utilization of healthy vegetables. Polyphenols, mineral elements, and antioxidant activity were analyzed in the leaves of six red pigmented lettuce (L.) cultivars; thereafter, we assessed the anti-tumor effects of cultivar B-2, which displayed the highest antioxidant activity. Quadrupole-Orbitrap mass spectrometry analysis revealed four classes of polyphenols in these cultivars. The composition and contents of these metabolites varied significantly among cultivars and primarily depended on leaf color. The B-2 cultivar had the highest antioxidant potential than others because it contained the highest levels of polyphenols, especially anthocyanin, flavone, and phenolic acid; furthermore, this cultivar displayed anti-tumor effects against the human lung adenocarcinoma cell line A549, human hepatoma cell line Bel7402, human cancer colorectal adenoma cell line HCT-8, and HT-29 human colon cancer cell line. Hence, the new red-leaf lettuce cultivar B-2 has a distinct metabolite profile, with high potential for development and utilization of natural phytochemical and mineral resources in lettuces and can be used as a nutrient-dense food product.

Int J Mol Sci. 2018 Apr 11 ;19(4). Epub 2018 Apr 11. PMID: 29641499

617
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Anti-inflammatory activity of extra virgin olive oil polyphenols.


BACKGROUND AND OBJECTIVE: Altered inflammatory response characterizes chronic immunemediated inflammatory diseases (IMID) such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, and psoriasis. Accumulating evidence indicates that regular consumption of extra virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, is associated with a reduced risk of developing chronic degenerative disorders such as cardiovascular diseases, type 2 diabetes and cancer. The beneficial effects on health of EVOO have been attributed, besides to the monounsaturated fats content, to the presence of phenolic compounds that have antioxidant, anti-inflammatory and immunomodulatory properties. The purpose of this review is to provide an overview of the effects of EVOO polyphenols on IMID highlighting the potential mechanisms of action.METHODS: Scientific papers were found by searching in PubMed up to May 2017 using the following key words: rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, and psoriasis also in combination with EVOO, phenolic compounds, oleuropein, oleocantal, hydroxytyrosol,tyrosol and oleochantal.RESULTS: In vitro and in vivo studies indicate that EVOO and its polyphenols can improve diseases symptoms in IMID, by acting both at local and systemic levels and by modulating several molecular pathways. Nevertheless, there are not sufficient data to achieve specific nutritional guidelines.CONCLUSION: Further research is needed to evaluate the real contribution of EVOO and its phenolic compounds in modulating the IMID-associated inflammatory perturbations, in order to develop appropriate nutritional recommendations.

Endocr Metab Immune Disord Drug Targets. 2018 ;18(1):36-50. PMID: 29141574

618
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Inhibition of cell cycle progression by the hydroxytyrosol-cetuximab combination yields enhanced chemotherapeutic efficacy.


Hydroxytyrosol (HT), a polyphenol of olive oil, downregulates epidermal growth factor (EGFR) expression and inhibits cell proliferation in colon cancer (CC) cells, with mechanisms similar to that activated by the EGFR inhibitor, cetuximab. Here, we studied whether HT treatment would enhance the cetuximab inhibitory effects on cell growth in CC cells. HT-cetuximab combination showed greater efficacy in reducing cell growth in HT-29 and WiDr cells at concentrations 10 times lower than when used as single agents. This reduction was clearly linked to cell cycle blockade, occurring at G/M phase. The cell cycle arrest in response to combination treatment is related to cyclins B, D1, and E, and cyclin-dependent kinase (CDK) 2, CDK4, and CDK6 down-regulation, and to the concomitant over-expression of CDK inhibitors p21 and p27. HT and cetuximab stimulated a caspase-independent cell death cascade, promotedtranslocation of apoptosis-inducing factor (AIF) from mitochondria to nucleus and activated the autophagy process. Notably, normal colon cells and keratinocytes were less susceptible to combo-induced cell death and EGFR downregulation. These results suggest a potential role of diet, containing olive oil, during cetuximab chemotherapy of colon tumor. HT may be a competent therapeutic agent in CC enhancing the effects of EGFR inhibitors.

Oncotarget. 2017 Oct 10 ;8(47):83207-83224. Epub 2017 Aug 24. PMID: 29137335

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These results support further testing of hydroxytyrosol for prostate cancer therapy.


SCOPE: Hydroxytyrosol (HT), a polyphenol from olives, is a potential anticancer agent. This study was designed to evaluate the anticancer activity of HT against prostate cancer cells, and the mechanism thereof.METHODS AND RESULTS: Treatment of LNCaP and C4-2 prostate cancer cells with HT resulted in a dose-dependent inhibition of proliferation. This was in contrast to HT's ineffectiveness against normal prostate epithelial cells RWPE1 and PWLE2, suggesting cancer-cell-specific effect. HT induced G1/S cell cycle arrest, with inhibition of cyclins D1/E and cdk2/4 and induction of inhibitory p21/p27. HT also induced apoptosis, as confirmed by flow cytometry, caspase activation, PARP cleavage, and BAX/Bcl-2 ratio. It inhibited the phosphorylation of Akt/STAT3, and induced cytoplasmic retention of NF-κB, which may explain its observed effects. Finally, HT inhibited androgen receptor (AR) expression and the secretion of AR-responsive prostate-specific antigen.CONCLUSION: Castration-resistant prostate cancers retain AR signaling and are often marked by activated Akt, NF-κB, and STAT3 signaling. Our results establish a pleiotropic activity of HT against these oncogenic signaling pathways. Combined with its nontoxic effects against normal cells, our results support further testing of HT for prostate cancer therapy.

Nutr Cancer. 2017 Aug-Sep;69(6):932-942. Epub 2017 Jul 18. PMID: 28718667

620
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Synergism between α-mangostin and TRAIL induces apoptosis in squamous cell carcinoma of the oral cavity.


Mangosteen (Garcinia mangostana) is a tree found in South-East Asia and the pericarp of its fruit has been used in folk medicine for the treatment of many human illnesses. Mangosteen fruit rinds contain a high concentration of xanthone, which is a type of polyphenol. One type of xanthone,α-mangostin, has been reported to exert chemopreventive effects against chemically-induced colon cancer through the decrease of c-Myc expression, suppressing tumor growth in a mouse model of mammary cancer. A recent study demonstrated the inhibitive effect of α-mangostin on the growth of prostatecancer. However, it remains unclear whether α-mangostin induces cell death in oral cancer. The present study examined the impact of α-mangostin on human oral squamous cell carcinoma (HOSCC). Firstly we analyzed the expression of c-Myc in five HOSCC cell lines. The highest expression level of c-MycmRNA was observed in SAS cells and the lowest in HSC-4 cells. Therefore, SAS cells were treated with α-mangostin, which was found to exert a weak cytocidal effect. Since α-mangostin has been reported to exert synergistic effects on cancers when combined with anticancer drugs, we attempted to evaluate such synergistic effects of α-mangostin when used with a cytokine, tumor necrosis factor (TNF)-related apoptosis‑inducing ligand (TRAIL). We found that the combination of α-mangostin with TRAIL induced apoptosis of SAS cells through the mitochondrial pathway via activation of caspase-9 and -3/7, following release of cytochrome c. This apoptosis was induced by S/G2/M-phase arrest. Immunopositivity for c-Myc was observed in the cytoplasm of tumor cells in 16 (40%) of the 40 cases of HOSCC. These data revealed that the combination of α-mangostin and TRAIL may have a considerablepotential for the treatment of oral cancer.

Oncol Rep. 2017 Dec ;38(6):3439-3446. Epub 2017 Oct 12. PMID: 29039600

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A review of the anticancer effects of rosemary extract and rosemary extract polyphenols.


Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival. Compounds of plant origin, including food components, have attracted scientific attention for use as agents for cancer prevention and treatment. The exploration into natural products offers great opportunity to evaluate new anticancer agents as well as understand novel and potentially relevant mechanisms of action. Rosemary extract has been reported to have antioxidant, anti-inflammatory, antidiabetic and anticancer properties. Rosemary extract contains many polyphenols with carnosic acid and rosmarinic acid found in highest concentrations. The present review summarizes the existing in vitro and in vivo studies focusing on the anticancer effects of rosemary extract and the rosemary extract polyphenols carnosic acid and rosmarinic acid, and their effects on key signaling molecules.

Nutrients. 2016 Nov 17 ;8(11). Epub 2016 Nov 17. PMID: 27869665

622
[+]

Carnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer.


BACKGROUND: In this study we investigated the in vitro and in vivo anticancer effect of carnosol, a naturally occurring polyphenol, in triple negative breast cancer.RESULTS: We found that carnosol significantly inhibited the viability and colony growth induced G2 arrest in the triple negative MDA-MB-231. Blockade of the cell cycle was associated with increased p21/WAF1 expression and downregulation of p27. Interestingly, carnosol was found to induce beclin1-independent autophagy and apoptosis in MDA-MB-231 cells. The coexistence of both events, autophagy and apoptosis, was confirmed by electron micrography. Induction of autophagy was found to be an early event, detected within 3 h post-treatment, which subsequently led to apoptosis. Carnosol treatment also caused a dose-dependent increase in the levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2). Moreover, we show that carnosol induced DNA damage, reduced the mitochondrial potential and triggered the activation of the intrinsic and extrinsic apoptotic pathway. Furthermore, we found that carnosol induced a dose-dependent generation of reactive oxygen species (ROS) and inhibition of ROS by tiron, a ROS scavenger, blocked the induction of autophagy and apoptosis and attenuated DNA damage. To our knowledge, this is the first report to identify the induction of autophagy by carnosol.CONCLUSION: In conclusion our findings provide strong evidence that carnosol may be an alternative therapeutic candidate against the aggressive form of breast cancer and hence deserves more exploration.

PLoS One. 2014 ;9(10):e109630. Epub 2014 Oct 9. PMID: 25299698

623
[+]

Polyphenols from the Mediterranean herb rosemary for prostate cancer.


The Mediterranean diet is rich in fruits and vegetables and has been associated with a variety of health benefits including cancer prevention. One aspect of the diet that has not received enough attention is Mediterranean herbs. Specifically, rosemary and its polyphenolic diterpenes (carnosic acid and carnosol) are known to possess anti-oxidant activity that may be beneficial for cancer control. Herein, we describe the in vitro and in vivo studies carried out towards understanding the molecular mechanisms of carnosic acid and carnosol leading to inhibition of prostate cancer. The reported findings suggest that these polyphenols target multiple signaling pathways involved in cell cycle modulation and apoptosis. Further work is required to understand its potential for health promotion and potential drug discovery for prostate cancer chemoprevention.

Front Pharmacol. 2013 ;4:29. Epub 2013 Mar 25. PMID: 23531917

624
[+]

Curcumin induced paraptosis in human glioblastoma cell line A172.


Curcumin is a polyphenol compound extracted from Curcuma longa plant, is a molecule with pleiotropic effects that suppresses transformation, proliferation and metastasis of malignant tumors. Curcumin can cause different kinds of cell death depending of its concentration on the exposed cell type. Here we show that exposure of the glioblastoma cell line A172 to curcumin at 50 μM, the IC50, causes morphological change characteristic of paraptosis cell-death. Vesicles derived from the endoplasmic reticulum (ER) and low membrane potential of the mitochondria were constantly found in the exposed cells. Furthermore, changes in expression of the ER Stress Response (ERSR) genes IRE1 and ATF6, and the microRNAs (miRNAs) miR-27a, miR-222, miR-449 was observed after exposure to curcumin. AKT-Insulin and p53-BCL2 networks were predicted being modulated by the affected miRNAs. Furthermore, AKT protein levels reduction was confirmed. Our data, strongly suggest that curcuminexerts its cell-death properties by affecting the integrity of the reticulum, leading to paraptosis in the glioblastoma cells. These data unveils the versatility of curcumin to control cancer progression.

Toxicol In Vitro. 2018 Apr 30 ;51:63-73. Epub 2018 Apr 30. PMID: 29723631

625
[+]

Genistein can significantly inhibit proliferation of hepatocellular carcinoma Hepa 1-6 cell line and induce apoptosis in this cell line.


Background: One of the main causes of mortality is hepatocellular carcinoma (HCC) which accounts for the third leading cause of deaths and one in forty deaths worldwide. The flavonoids, natural antioxidant compounds, account for a major group of polyphenolic compounds. One of the major isoflavones in soybean is genistein (GE) which can inhibit proliferation and induce apoptosis. Isoflavones, major type of phenolic materials, derived from dietary plants and medicinal herbs play a significant role in cancer prevention and treatment. Correlation between dietary habits and cancer risk including breast, prostate, and colon cancer has been reported. Various bioactivities of these compounds such as anticarcinogenic and antioxidant are responsible for their chemopreventive activities by which induce migration, proliferation, cell cycle arrest, and apoptosis. GE, one of the major isoflavones, is considered as a potent chemopreventive agent against cancer. The aim of this study was to investigate the inhibitory and apoptotic effects of GE on HCC Hepa1-6 cell line.Methods: Cell viability assay and cell cycle analysis with flow cytometry were used to evaluate proliferative and apoptotic effect GE.Results: GE inhibited the growth of Hepa1-6 cells and induced apoptosis with a concentration and time-dependent fashion. During GE treatment for 24, the half maximal inhibitory concentration (IC50) was 20μM, and the maximum inhibition of cell growth was 52% (

Int J Prev Med. 2018 ;9:12. Epub 2018 Feb 8. PMID: 29541427

626
[+]

Resveratrol inhibits ROS-promoted activation and glycolysis of pancreatic stellate cells via suppression of miR-21.


Activation of pancreatic stellate cells (PSCs) initiates pancreatic fibrosis in chronic pancreatitis and furnishes a niche that enhances the malignancy of pancreatic cancer cells (PCCs) in pancreatic ductal adenocarcinoma (PDAC). Resveratrol (RSV), a natural polyphenol, exhibits potent antioxidant and anticancer effects. However, whether and how RSV influences the biological properties of activated PSCs and the effects of these changes on tumor remain unknown. In the present study, we found that RSV impeded hydrogen peroxide-driven reactive oxygen species- (ROS-) induced activation, invasion, migration, and glycolysis of PSCs. In addition, miR-21 expression in activated PSCs was downregulated after RSV treatment, whereas the PTEN protein level increased. miR-21 silencing attenuated ROS-induced activation, invasion, migration, and glycolysis of PSCs, whereas the overexpression of miR-21 rescued the responses of PSCs treated with RSV. Moreover, RSV or N-acetyl-L-cysteine (NAC) administration or miR-21 knockdown in PSCs reduced the invasion and migration of PCCs in coculture, and the effects of RSV were partly reversed by miR-21 upregulation. Collectively, RSV inhibits PCC invasion and migration through suppression of ROS/miR-21-mediated activation and glycolysis in PSCs. Therefore, targeting miR-21-mediated glycolysis by RSV in tumor stroma may serve as a new strategy for clinical PDAC prevention or treatment.

Oxid Med Cell Longev. 2018 ;2018:1346958. Epub 2018 Apr 26. PMID: 29854071

627
[+]

Epigallocatechin gallate, ellagic acid, and rosmarinic acid inhibit the proliferation of human HL-60 promyelocytic leukemia cells.


Epigallocatechin gallate (EGCG), ellagic acid (EA) and rosmarinic acid (RA) are natural polyphenols exerting cancer chemopreventive effects. Ribonucleotide reductase (RR; EC 1.17.4.1) converts ribonucleoside diphosphates into deoxyribonucleoside diphosphates being essential for DNA replication, which is why the enzyme is considered an excellent target for anticancer therapy. EGCG, EA, and RA dose-dependently inhibited the growth of human HL-60 promyelocytic leukemia cells, exerted strong free radical scavenging potential, and significantly imbalanced nuclear deoxyribonucleoside triphosphate (dNTP) concentrations without distinctly affecting the protein levels of RR subunits (R1, R2, p53R2). Incorporation of (14)C-cytidine into nascent DNA of tumor cells was also significantly lowered, being equivalent to an inhibition of DNA synthesis. Consequently, treatment with EGCG and RA attenuated cells in the G0/G1 phase of the cell cycle, finally resulting in a pronounced induction of apoptosis. Sequential combination of EA and RA with the first-line antileukemic agent arabinofuranosylcytosine (AraC) synergistically potentiated the antiproliferative effect of AraC, whereas EGCG plus AraC yielded additive effects. Taken together, we show for the first time that EGCG, EA, and RA perturbed dNTP levels and inhibited cell proliferation in human HL-60 promyelocytic leukemia cells, with EGCG and RA causing a pronounced induction of apoptosis. Due to these effects and synergism with AraC, these food ingredients deserve further preclinical and in vivo testing as inhibitors of leukemic cell proliferation.

Phytomedicine. 2015 Jan 15 ;22(1):213-22. Epub 2014 Dec 3. PMID: 25636891

628
[+]

Ellagic acid encapsulated chitosan nanoparticles for drug delivery system in human oral cancer cell line.


Ellagic acid (EA), a naturally occurring polyphenolic compound is well documented for its anticancer property in numerous pre-clinical models. The properties like poor water solubility and limited oral bio-availability of ellagic acid has hampered its clinical applications. The present study, reports the preparation of ellagic acid encapsulated chitosan nanoparticles (EA@CS-NP) by ionic gelation method as an effective drug delivery for oral cancer treatment. The synthesized ellagic acid nanoparticle is spherical shaped with an average particle size of 176nm. The drug-encapsulation and loading-efficiency of the nanoparticles were 94±1.03% and 33±2.15% respectively. The in vitro drug release profile in the PBS medium shows sustained release of EA from EA@CS-NP. Further, this study evaluates the therapeutic efficacy of EA@CS-NP in human oral cancer cell line (KB) using MTT and DNA fragmentation analysis. EA@CS-NP exhibit significant cytotoxicity in KB cells in a dose-dependent manner with a very low IC50 value compared to the free EA. The results of the present study strengthen our hypothesis and hope that this novel formulation could possibly overcome the current limitations of ellagic acid and can open a new avenue fororal cancer therapy.

Colloids Surf B Biointerfaces. 2013 Oct 1 ;110:313-20. Epub 2013 May 2. PMID: 23732810

629
[+]

A comprehensive review on the chemotherapeutic potential of piceatannol for cancer treatment, with mechanistic insights.


Cancer is a diverse class of diseases characterized by uncontrolled cell growth that constitutes the greatest cause of mortality and morbidity worldwide. Despite steady progress, the treatment modalities of cancer are still insufficient. Several new concepts have emerged for therapeutic intervention in malignant diseases with the goal of identifying specific targets and overcoming resistance against current cytotoxic therapies. Many studies have reported the remarkable and significant properties of dietary plant polyphenols such as curcumin, resveratrol, flavopiridol, indirubin, magnolol, piceatannol, parthenolide, epigallocatechin gallate, and cucurbitacin as anticancer agents known for their pleiotropic effects on cancer, immune cells, and inflammation. Piceatannol, an analogue and metabolite of resveratrol, is a natural stilbene commonly found in grape skins and wine. Compared to resveratrol, this molecule exhibits superior bioactivities as an inhibitor of COX-1/2 and the CSN-associated kinase. Piceatannol is thought to be a potent natural compound with many therapeutic effects, such as the prevention of hypercholesterolemia, arrhythmia, atherosclerosis, angiogenesis, and cardiovascular diseases. It also demonstrates vasorelaxation, antioxidant, and anticancer activities. This comprehensive review summarizes the current data regarding the mechanisms of action of piceatannol, its chemopreventive properties, and its possible therapeutic potential against various types of human cancer.

J Agric Food Chem. 2016 Feb 3 ;64(4):725-37. Epub 2016 Jan 26. PMID: 26758628

630
[+]

Piceatannol inhibits migration and invasion of prostate cancer cells.


Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol detected in grapes, red wine and Rheum undulatum; it has also been demonstrated to exert anticarcinogenic effects. In this study, in order to determine whether piceatannol inhibits the lung metastasis of prostate cancer cells, MAT-Ly-Lu (MLL) rat prostate cancer cells expressing luciferase were injected into the tail veins of male nude mice. The oral administration of piceatannol (20 mg/kg) significantly inhibited the accumulation of MLL cells in the lungs of these mice. In the cell culture studies, piceatannol was demonstrated to inhibit the basal and epidermal growth factor (EGF)-induced migration and invasion of DU145 cells, in addition to the migration of MLL, PC3 and TRAMP-C2 prostate cancer cells. In DU145 cells, piceatannol attenuated the secretion and messenger RNA levels of matrix metalloproteinase-9, urokinase-type plasminogen activator (uPA) and vascular endothelial growth factor (VEGF). Piceatannol increased the protein levels of tissue inhibitor of metalloproteinase-2 in a concentration-dependent fashion. Additionally, piceatannol inhibited the phosphorylation of signal transducer and activator of transcription (STAT) 3. Furthermore, piceatannol effected reductions in both basal and EGF-induced interleukin (IL)-6 secretion. An IL-6 neutralizing antibody inhibited EGF-induced STAT3 phosphorylation and EGF-stimulated migration of DU145 cells. Interleukin-6 treatment was also shown to enhance the secretion of uPA and VEGF, STAT3 phosphorylation and the migration of DU145 cells; these increases were suppressed by piceatannol. These results demonstrate that the inhibition of IL-6/STAT3 signaling may constitute a mechanism by which piceatannol regulates the expression of proteins involved in regulating the migration and invasion of DU145 cells.

J Nutr Biochem. 2012 Mar ;23(3):228-38. Epub 2011 Apr 15. PMID: 21497499

631
[+]

Piceatannol induces apoptosis in DU145 human prostate cancer cells.


Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene) is a polyphenol that is found in grapes, red wine, Rheum undulatum, and the seeds of Euphorbia lagascae. It has been previously reported that piceatannol inhibits the proliferation of a variety of cancer cell types. In the present study, we assessed the effects of piceatannol on the growth of androgen-insensitive DU145 prostate cancer cells at concentrations of 1-10 micromol/L. Piceatannol reduced the viable numbers and increased the numbers of apoptotic DU145 cells in a dose-dependent manner. Western blot analysis revealed that piceatannol increased the protein levels of cleaved caspase-8, -9, -7, and -3 and cleaved poly(ADP-ribose) polymerase (PARP). Piceatannol increased mitochondrial membrane permeability and cytochrome c release from the mitochondria to the cytosol. Piceatannol induced an increase in the levels of truncated Bid, Bax, Bik, Bok, and Fas but caused a decrease in the levels of Mcl-1 and Bcl-xL. Caspase-8 and -9 inhibitors mitigated piceatannol-induced apoptosis. The caspase-8 inhibitor suppressed the piceatannol-induced cleavage of Bid, caspase-3, and PARP. These results indicate that piceatannol induces apoptosis via the activation of the death receptor and mitochondrial-dependent pathways in prostate cancer cells.

J Med Food. 2009 Oct ;12(5):943-51. PMID: 19857055

632
[+]

Piceatannol inhibits proliferation of human bladder cancer cells.


Piceatannol (3,3',4,5'-Tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine. Piceatannol is a protein kinase inhibitor that modifies multiple cellular targets exerting immunosuppressive, antileukemic, and antitumorigenic activities in several cell lines and animal models. In this study, the antiproliferative activity of piceatannol was investigated. The results showed that piceatannol inhibited the proliferation of T24 and HT1376 human bladder cancer cells by blocking cell cycle progression in the G0/G1 phase and inducing apoptosis. ELISA showed that the G0/G1 phase arrest is due to an increased in the expression of p21/WAF1. An enhancement in Fas/APO-1 and membrane-bound Fas ligand (mFasL) might be responsible for the apoptotic effect induced by piceatannol. Our study reports the novel finding, that the induction of p21/WAF1 and activity of the Fas/mFasL apoptotic system may participate in the antiproliferative activity of piceatannol in T24 and HT1376 cells.

Mol Nutr Food Res. 2008 Apr ;52(4):408-18. PMID: 18381677

633
[+]

Inhibition of tumor progression by oral piceatannol in mouse 4T1 mammary cancer is associated with decreased angiogenesis and macrophage infiltration.


Piceatannol, a polyphenol which exhibits anticancer activities, is found in grapes, red wine and berries. It has been shown to inhibit several transcription factor pathways. The present study was conducted to determine whether oral administration of piceatannol inhibits mammary tumor progression. 4T1 mammary carcinoma cells were injected into the mammary fat pad of syngeneic female BALB/c mice. Starting 1 day later, piceatannol (10- or 20-mg/kg body weight/day) was administered by oral gavage for 30 days. Piceatannol treatment reduced tumor growth. In tumor tissues, piceatannol treatment reduced the expression of transcription factors P-NFκB p65, P-STAT3 and HIF-1α and multiple proteins involved in regulation of cell cycle progression (Ki67, cyclin D1, cyclin A, CDK2, CDK4), angiogenesis (VEGF-A, VEGFR-2, VE-cadherin, CD31) and lymphangiogenesis (VEGF-C, LYVE-1), as well as macrophage infiltration. Piceatannol significantly increased apoptotic cells and expression of both Bax and cleaved caspase-3 but reduced Bcl-2 expression in tumor tissues. In addition, piceatannol reduced the number and volume of pulmonary tumor nodules and expression of MMP-9 in both lung and tumor. It also reduced tissue levels of cytokines/chemokines,including M-CSF and MCP-1. In vitro results revealed that piceatannol inhibited migration of 4T1 cells and monocytes, as well as secretion of MCP-1 and M-CSF by 4T1 cells. 4T1 cell-conditioned medium stimulated monocyte migration, which was suppressed by a CCR2 antibody. These results indicate thatalteration in tumor microenvironment (macrophages, transcription factors, etc.) is an important mechanism by which piceatannol inhibits tumor proliferation, angiogenesis and lymphangiogenesis, leading to suppression of mammary tumor growth and metastasis.

J Nutr Biochem. 2015 Nov ;26(11):1368-78. Epub 2015 Jul 26. PMID: 26297476

634
[+]

A review of the therapeutic potential of piceatannol in metabolic diseases.


Metabolic disease comprises a set of risk factors highly associated with obesity and insulin resistance and is a consequence of central adiposity, hyperglycemia, and dyslipidemia. Furthermore, obesity increases the risk of the development of metabolic disease due to ectopic fat deposition, low-grade inflammation, and systemic energy disorders caused by dysregulated adipose tissue function. Piceatannol is a naturally occurring polyphenolic stilbene found in various fruits and vegetables and has been reported to exhibit anticancer and anti-inflammatory properties. In addition, recently reported beneficial effects of piceatannol on hypercholesterolemia, atherosclerosis, and angiogenesis underscore its therapeutic potential in cardiovascular disease. However, investigation of its role in metabolic disease is still in its infancy. This review intensively summarizes in vitro and in vivo studies supporting the potential therapeutic effects of piceatannol in metabolic disease, including inhibition of adipogenesis and lipid metabolism in adipocytes, and regulation of hyperlipidemia, hyperglycemia, insulin resistance, and fatty acid-induced inflammation and oxidative stress.

J Med Food. 2017 May ;20(5):427-438. Epub 2017 Apr 7. PMID: 28387565

635
[+]

Myricetin is a novel natural inhibitor of neoplastic cell transformation and MEK1.


Evidence suggests that mitogen-activated protein kinase kinase (MEK) plays a role in cell transformation and tumor development and might be a significant target for chemoprevention. 3,5,4'-Trihydroxy-trans-stilbene (resveratrol), a non-flavonoid polyphenol found in various foods and beverages, including red wines, is reported to be a natural chemopreventive agent. However, the concentrations required to exert these effects might be difficult to achieve by drinking only one or two glasses of red wine a day. On the other hand, the flavonol content of red wine is approximately 30 times higher than that of resveratrol. Here we demonstrated that 3,3',4',5,5',7-hexahydroxyflavone (myricetin), one of the major flavonols in red wine, is a novel inhibitor of MEK1 activity and transformation of JB6 P+ mouse epidermal cells. Myricetin (10 microM) inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA) or epidermal growth factor (EGF)-induced cell transformation by 76 or 72%, respectively, compared with respective reductions of 26 or 19% by resveratrol (20 microM). A combination of myricetin and resveratrol exerted additive but not synergistic effects on either TPA- or EGF-induced transformation. Myricetin, but not resveratrol, attenuated tumor promoter-induced activation of c-fos or activator protein-1. Myricetin strongly inhibited MEK1 kinase activity and suppressed TPA- or EGF-induced phosphorylation of extracellular signal-regulated kinase (ERK) or p90 ribosomal S6 kinase, downstream targets of MEK. Moreover, myricetin inhibited H-Ras-induced cell transformation more effectively than either PD098059, a MEK inhibitor, or resveratrol. Myricetin directly bound with glutathione S-transferase-MEK1 but did not compete with ATP. Overall, these results indicated that myricetin has potent anticancer-promoting activity and mainly targets MEK signaling, which may contribute to the chemopreventive potential of several foods including red wines.

Carcinogenesis. 2007 Sep ;28(9):1918-27. Epub 2007 Aug 11. PMID: 17693661

636
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Resveratrol prevents p53 aggregation in vitro and in breast cancer cells.


One potential target for cancer therapeutics is the tumor suppressor p53, which is mutated in more than 50% of malignant tumors. Loss of function (LoF), dominant negative (DN) and gain of function (GoF) mutations in p53 are associated with amyloid aggregation. We tested the potential of resveratrol, a naturally occurring polyphenol, to interact and prevent the aggregation of wild-type and mutant p53using fluorescence spectroscopy techniques and in human breast cancer cells (MDA-MB-231, HCC-70 and MCF-7) using immunofluorescence co-localization assays. Based on our data, an interaction occurs between resveratrol and the wild-type p53 core domain (p53C). In addition, resveratrol and its derivatives pterostilbene and piceatannol inhibit mutant p53C aggregation. Additionally, resveratrol reduces mutant p53 protein aggregation in MDA-MB-231 and HCC-70 cells but not in the wild-type p53 cell line MCF-7. To verify the effects of resveratrol on tumorigenicity, cell proliferation and cell migration assays were performed using MDA-MB-231 cells. Resveratrol significantly reduced the proliferative and migratory capabilities of these cells. Our study provides evidence that resveratrol directly modulates p53, enhancing our understanding of the mechanisms involved in p53 aggregation and its potential as a therapeutic strategy for cancer treatment.

Oncotarget. 2018 Jun 26 ;9(49):29112-29122. Epub 2018 Jun 26. PMID: 30018739

637
[+]

Apple polyphenol inhibited the vitality, cell growth and proliferation, and migration of breast cancer cells MDA-MB-231


OBJECTIVE: To investigate the effects of apple polyphenol on cell proliferation and migration of breast cancer cell line MDA-MB-231, and explore the potential mechanism.METHODS: The breast cancer cells in the logarithmic phase were treated with 0, 50, 100, 200, 400 and 800μg/m L of apple polyphenol for 24, 48 and 72 h, then Trypan blue staining was employed to detect cell vitality; CCK8 kit was used to determine cell growth and proliferation; cell migration ability was observed by scratch experiment, and the change of proteins expression level was assessed by Western blot.RESULTS: Apple polyphenol could content-dependently inhibit breast cancer cell's vitality and proliferation between 0 and 800μg/m L, decrease the proteins level of ubiquitinlike with PHD and ring finger domain 1( UHRF1) and matrix metalloproteinases-2( MMP2), and the protein levels of DNA methyltransferases 3 a( DNMT3 a) and DNMT3 b, themolecular targets of UHRF1, also decreased. Apple polyphenol inhibition of cell 's migration was more significant between 400 and 800 μg/mL.CONCLUSION: Apple polyphenol inhibited the vitality, cell growth and proliferation, and migration of breast cancer cells MDA-MB-231 by decreasing the proteins expression of UHRF1 and MMP2, and the downstream targets of UHRF1, DNMT3 a and DNMT3 b, also decreased.

Wei Sheng Yan Jiu. 2017 Nov ;46(6):960-964. PMID: 29903207

638
[+]

These results suggest that curcumin controls hST8Sia I gene expression via AMPK signal pathway in A549 cells.


Curcumin, a natural polyphenolic compound isolated from the plant, is known to induce autophagy in various cancer cells, including lung cancer. In the present study, we also confirmed by LC3 immunofluorescence and immunoblotting analyses that curcumin triggers autophagy in the human lung adenocarcinoma A549 cell line. In parallel with autophagy induction, the gene expression of human GD3 synthase (hST8Sia I) responsible for ganglioside GD3 synthesis was markedly elevated in response to curcumin in the A549 cells. To investigate the transcriptional activation of hST8Sia I associated with the autophagy formation in curcumin-treated A549 cells, functional characterization of the 5'-flanking region of the hST8Sia I gene was carried out using the luciferase reporter assay system. Deletion analysis demonstrated that the -1146 to -646 region, which includes the putative c-Ets-1, CREB, AP-1, and NF-κB binding sites, functions as the curcumin-responsive promoter of hST8Sia I in A549 cells. The site-directed mutagenesis and chromatin immunoprecipitation assay demonstrated that the NF-κB binding site at -731 to -722 was indispensable for the curcumin-induced hST8Sia I gene expression in A549 cells. Moreover, the transcriptional activation of hST8Sia I by the curcumin A549 cells was strongly inhibited by compound C, an inhibitor of AMP-activated protein kinase (AMPK). These results suggest that curcumin controls hST8Sia I gene expression via AMPK signal pathway in A549 cells.

Int J Mol Sci. 2018 Jul 2 ;19(7). Epub 2018 Jul 2. PMID: 30004453

639
[+]

A review of the anti-oxidative polyphenolic compounds of cocoa.


Oxidative stress plays a key role in the pathogenesis of different serious chronic diseases such as cancer, diabetes, cardiovascular and neurodegenerative disorders, etc. Recent research has been focused on the beneficial role of dietary antioxidants against oxidative stress both under in vitro and in vivo conditions. Theobroma cacao L. (cacao tree) is an evergreen tree which is native to South America. It is a plant of great economic importance and its seeds are commonly used to produce cocoa powder and chocolate. In addition to its uses in food industry, cocoa is a rich source of polyphenolic antioxidants. There is a plethora of in vitro and in vivo studies that report cocoa antioxidant capacity. The protective activity of cocoa seems to be due to its phytochemical constituents, especially catechins. However, bioavailability of cocoa polyphenolic constituents following oral administration is very low (nanomolar concentrations). In the present paper, we critically reviewed the available literature on the antioxidant and free radical scavenging activities of cocoa and its polyphenolic constituents. In addition to these, we provide brief information about cultivation, phytochemistry, bioavailability and clinical impacts of cocoa.

Curr Pharm Biotechnol. 2015 ;16(10):891-901. PMID: 26059107

640
[+]

Resveratrol inhibits HSP27 expression and sensitizes breast cancer cells to doxorubicin therapy.


The use of chemopreventive natural compounds represents a promising strategy in the search for novel therapeutic agents in cancer. Resveratrol (3,4',5-trans-trihydroxystilbilene) is a dietary polyphenol found in fruits, vegetables and medicinal plants that exhibits chemopreventive and antitumor effects. In this study, we searched for modulated proteins with preventive or therapeutic potential in MCF-7 breast cancer cells exposed to resveratrol. Using two-dimensional electrophoresis we found significant changes (FC>2.0; p≤0.05) in the expression of 16 proteins in resveratrol-treated MCF-7 cells. Six down-regulated proteins were identified by tandem mass spectrometry (ESI-MS/MS) as heat shock protein 27 (HSP27), translationally-controlled tumor protein, peroxiredoxin-6, stress-induced-phosphoprotein-1, pyridoxine-5'-phosphate oxidase-1 and hypoxanthine-guanine phosphoribosyl transferase; whereas one up-regulated protein was identified as triosephosphate isomerase. Particularly, HSP27 overexpression has been associated to apoptosis inhibition and resistance of human cancer cells to therapy. Consistently, we demonstrated that resveratrol induces apoptosis in MCF-7 cells. Apoptosis was associated with a significant increase in mitochondrial permeability transition, cytochrome c release in cytoplasm, and caspases -3 and -9 independent cell death. Then, we evaluated the chemosensitization effect of increasing concentrations of resveratrol in combination with doxorubicin anti-neoplastic agent in vitro. We found that resveratrol effectively sensitize MCF-7 cells to cytotoxic therapy. Next, we evaluated the relevance of HSP27 targeted inhibition in therapy effectiveness. Results evidenced that HSP27 inhibition using RNA interference enhances the cytotoxicity of doxorubicin. In conclusion, our data indicate that resveratrol may improve the therapeutic effects of doxorubicin in part by cell death induction. We propose that potential modulation of HSP27 levels using natural alternative agents, as resveratrol, may be an effective adjuvant in breast cancer therapy.

PLoS One. 2013 ;8(5):e64378. Epub 2013 May 27. PMID: 23724044

641
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The results of this review suggest that açaí is safe and can be used as a chemoprotective agent against cancer development.


Cancer is an increasingly frequent malignancy worldwide, and despite the advances in drug development, it is still necessary to develop new plant-derived medicines. Euterpe oleracea (açaí) is abundant in South and Central America and has health benefits due to its high levels of phytochemicals, including lignans and polyphenols. The aim of this review was to systematically describe the safety and antitumor effects of açaí in preclinical models using rodents to provide a morecomprehensive assessment of açaí for both therapeutic uses and the development of future clinical studies in cancer. Eligible studies were identified using four international databases (PubMed, Medline, Lilacs and SciELO) from their inception date through December 2017. The included studies were analyzed with methodological rigor (QATRS) to enable better quality control for these experimental studies. Sixty publications were identified in the databases, but only 9 articles were eligible: 6 evaluated the pharmacological effects of açaí in animal models of cancer (1 model each of esophagealcancer, urothelial cancer, melanoma and Walker-256 tumor and 2 models of colon cancer), and 3 were toxicological assays using preclinical models with rodents. Overall, 747 animals were analyzed. On a QATRS score scale of 0-20, the quality of the studies ranged from 16 to 20 points. Pulp was the mainfraction of açaí administered, and an oral administration route was most common. The açaí dosage administered by gavage ranged from 30 mg/kg to 40,000 mg/kg, and açaí fed in the diet accounted for 2.5% to 5% of the diet. The anticarcinogenic and chemopreventive activities of açaí were observed in all experimental models of cancer and reduced the incidence, tumor cell proliferation, multiplicity and size of the tumors due to the antiinflammatory, antiproliferative and proapoptotic properties of açaí. No genotoxic effects were observed after açaí administration. The results of thisreview suggest that açaí is safe and can be used as a chemoprotective agent against cancer development. Açaí therapy may be a novel strategy for treating cancer.

PLoS One. 2018 ;13(7):e0200101. Epub 2018 Jul 2. PMID: 29966007

642
[+]

Chemopreventive properties of raisins originating from Greece in colon cancer cells.


Colorectal cancer is one of the major causes of cancer-related mortality in humans in both developed and developing countries. Dietary patterns influence the risk of colon cancer development, while plant-derived foods have gained great interest, due to the high content of antioxidants. Corinthian raisins (Currants, CR) and Sultanas (S) (Vitis vinifera L., Vitaceae) are dried vine fruits produced in Greece with many culinary uses in both the Mediterranean and the Western nutrition. In the present study, we investigated the effects of CR and S on human colon cancer cells. Methanol extracts of CR and S were used at different concentrations. The total polyphenol content and anti-radical activity were measured by Folin-Ciocalteu and DPPH, respectively. Antioxidant, anti-inflammatory and anti-proliferative effects on HT29 cell culture were evaluated. All extracts exhibited DPPH˙ scavenging activity in a dose-dependent manner. Both products suppressed cell proliferation, while the levels of glutathione and cyclooxygenase 2 were significantly decreased. A significant reduction in IL-8 levels and NF-kappaB p65 activation was also observed. Both antioxidant and anti-inflammatory effects were dependent on the duration of exposure. Results indicate that the methanol extracts of CR and S exhibit anti-radical activity in vitro, as well as cancer preventive efficacy on colon cancer cells, with S having slightly higher activity. The beneficial properties of these unique dried grapes are attributed to their high content of phenolic compounds.

Food Funct. 2013 Feb 26 ;4(3):366-72. PMID: 23211994

643
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This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells.


A major part of the wineries' wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts' use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods. Afterwards, the grape stem extracts were examined for their ability to inhibit growth of colon (HT29), breast (MCF-7 and MDA-MB-23), renal (786-0 and Caki-1) and thyroid (K1) cancer cells. The cancer cells were exposed to the extracts for 72 h and the effects on cell growth were evaluated using the SRB assay. The results indicated that all extracts inhibited cell proliferation, with IC₅₀ values of 121-230 μg/ml (MCF-7), 121-184 μg/ml (MDA-MD-23), 175-309 μg/ml (HT29), 159-314 μg/ml (K1), 180-225 μg/ml (786-0) and 134->400μg/ml (Caki-1). This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells.

Toxicol Lett. 2014 Oct 15 ;230(2):218-24. Epub 2014 Feb 6. PMID: 24508987

644
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Grape stem extracts at low concentrations inhibited the growth of HepG2 and HeLa cancer cells.


Grape extracts and wine have been studied widely due to their beneficial effects on human health. However, there are only few studies from grape stems extracts. Therefore, the main objective of the present study was the assessment in stem extracts from Greek Vitis vinifera varieties of the total polyphenolic content (TPC), the identification of the polyphenols present in them, and the evaluation of their antioxidant activity, protection against ROS-induced DNA damage and inhibition of liver (HepG2) and cervical (HeLa) cancer cell growth. The range of the TPC in grape stem extracts was from 345 to 584 mg GAE/g dry weight. Moreover, stem extracts contained different classes of polyphenols as flavonols, flavanols, procyanidins, phenolic acids and stilbenes. In DPPH and ABTS assays, the IC50 values of the stem extracts had an average of 7.8± 2.8 and 5.4 ± 2.6 μg/mL respectively. Also, all stem extracts inhibited OH- and ROO-induced DNA damage dose dependent with average IC50 values of 478 ± 217 and 1.15 ± 0.85 μg/mL respectively. Furthermore, stem extracts inhibited at low concentrations the growth of HepG2 and HeLa cancer cellswith average IC50 values of 50 ± 12 and 32 ± 16 μg/mL respectively. The above activities of grape stem extracts were comparable to those of seed extracts.

Food Chem Toxicol. 2013 Nov ;61:60-8. Epub 2013 Feb 1. PMID: 23380202

645
[+]

Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-κB signaling.


AIMS: TRAIL is a promising anticancer agent that has the potential to sensitize a wide variety of cancer or transformed cells by inducing apoptosis. However, resistance to TRAIL is a growing concern. Current manuscript aimed to employ combination treatment to investigate resveratrol induced TRAIL sensitization in NSCLC.METHOD: A549 and HCC-15 cells were used in an experimental design. Cell viability was determined by morphological image, crystal violet staining and MTT assay. Apoptosis was evaluated by LDH assay, Annexin V and DAPI staining. Autophagy and apoptosis indicator protein were examined by western blotting. TEM and puncta assay was carried out to evaluate the autophagy. MTP and ROS activity was evaluated by JC-1 and HDCFDA staining.FINDINGS: Resveratrol is a polyphenolic compound capable of activation of tumor suppressor p53 and its pro-apoptotic modulator PUMA. Herein, we showed the p53-independent apoptosis by decrease the expression of phosphorylated Akt-mediated suppression of NF-κB that is also substantiated with the downregulation of anti-apoptotic factors Bcl-2 and Bcl-xl in NSCLC, resulting in an attenuation of TRAIL resistance in combined treatment. Furthermore, apoptosis was induced in TRAIL-resistant lung cancer cells with a co-treatment of resveratrol and TRAIL assessed by the loss of MMP, ROS generations which resulting the translocation of cytochrome c from the mitochondria into the cytosol due to mitochondrial dysfunction. Moreover, autophagy flux was not affected by resveratrol-induced TRAIL-mediated apoptosis in NSCLC.SIGNIFICANCE: Overall, targeting the NF-κB (p65) pathway via resveratrol attenuates TRAIL resistance and induces TRAIL-mediated apoptosis which could be the effective TRAIL-based cancer therapy regimen.

Life Sci. 2018 Sep 1 ;208:208-220. Epub 2018 Jul 19. PMID: 30031063

646
[+]

EGCG inhibits cancer stem cells-like properties through targeting miR-485/CD44 axis in A549-cisplatin resistant cells.


Non-small cell lung cancer (NSCLC) remains one of the most aggressive tumors with low life expectancy worldwide. The existence of cancer stem cells (CSCs) contributes to the failure of cancer treatment resulted from drug resistance. Altered microRNA expression has been observed in human tumors due to its role in tumor growth, progression and metastasis. Hence, the aim of our present study was to investigate the effects of miR-485 on the CSC-like traits in NSCLC A549-cisplatin resistant cells and concentrate on the underlying molecular mechanism. It was found that CSC-like phenotypes were much more enriched in A549/cisplatin (A549/CDDP) cells compared to A549-parental cells. In addition, we observed that miR-485 was greatly decreased in A549/CDDP cells and miR-485 overexpression was able to decrease the stemness of A549/DDP cells. Meanwhile, epigallocatechin-3-gallate (EGCG), a green tea polyphenol which has been identified as an effective anticancer compound was able to increase miR-485 expression dose-dependently in A549/CDDP cells. Inhibitors of miR-485 remarkably increased CSC-like phenotypes, which could be reversed by indicated doses of EGCG. Moreover, CD44 was predicted as downstream target of miR-485 and the correlation between them was validated by performing dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Subsequently, in vivo experiments were employed to confirm that EGCG restrained CSC-like characteristics by increasing miR-485 and decreasing CD44 expression. Taken together, it was implied that stemness features and CSC population were suppressed by EGCG-modulated miR-485/CD44 axis in A549/CDDP cells. This article is protected by copyright. All rights reserved.

Mol Carcinog. 2018 Sep 4. Epub 2018 Sep 4. PMID: 30182373

647
[+]

This review highlights new evidence on the health-promoting properties of walnuts and their main micronutrient components.


PURPOSE OF REVIEW: Nuts in general and walnuts in particular are in the limelight for the association of their consumption with improved health outcomes. Walnuts have an optimal composition in bioactive nutrients and recent clinical and experimental studies have uncovered a number of beneficial effects of walnut micronutrients, working in isolation or in concert, on metabolic pathways and clinical outcomes that make this review timely and relevant.RECENT FINDINGS: Alpha-linolenic acid, a critical walnut component, is metabolized into bioactive oxylipins, has been shown to protect microglial cells from inflammation, and is associated with lower fatal myocardial infarction rates through a putative antiarrhythmic effect. Phytosterols relate to the cholesterol-lowering effect of nut consumption. Nonsodium minerals are associated with better cardiometabolic health. Walnut phytomelatonin has anticancer effects that are shared by the main walnut polyphenols and their metabolites, ellagitannins and urolithins, respectively.SUMMARY: This review highlights new evidence on the health-promoting properties of walnuts and their main micronutrient components. The conclusion is that walnuts are optimal healthful foods.

Curr Opin Clin Nutr Metab Care. 2018 Sep 7. Epub 2018 Sep 7. PMID: 30199393

648
[+]

A review of the phytochemical, anti-diabetic and cardiovascular properties of nettle.


Type 2 diabetes mellitus (DM) and cardiovascular diseases (CVD) have become the main cause of morbidity and death worldwide. In addition, current anti-diabetic and cardiovascular therapy is based on conventional drugs that have limited effectiveness and adverse side effects. In this regard, the role of medicinal herbs as a complementary or an alternative medicine is of great interest. Urtica dioica L. (Urticaceae), which is the focus of this review, has been widely used in traditional medicine to treat a variety of ailments, including, diabetes, hypertension and prostate cancer. The aim of this article is to review current knowledge related to the anti-diabetic and cardiovascular properties of U. dioica, with particular emphasis on the bioactive compounds, the plant parts used, and the action mechanism behind lowering blood glucose level and reducing risk of CVD. We also discuss the chemical composition and toxicological properties of the plant. From this review, it was suggested that the anti-diabetic and the cardiovascular effects of U. dioica are attributed to different classes of compounds, such as polyphenols, triterpens, sterols,flavonoids, and lectin which reduce the blood glucose level and the risk of CVD by their antihypertensive, antioxidant and anti-inflammatory properties and/or by interfering with different cellular signalization pathways, including increase of NO, inhibition of α-amylase and α-glycosidase, modulation of GLUT4 and protection of pancreatic β-cells, among others. The identification of the plant constituents and the understanding of their exact action mechanisms are necessary to prove the efficacy of the plant and develop it as pharmacological drug.

Mini Rev Med Chem. 2018 Sep 24. Epub 2018 Sep 24. PMID: 30246639

649
[+]

Assessment of effects of phenolic fractions from leaves and petals of dandelion in selected components of hemostasis.


Aerial parts and roots of Taraxacum officinale (dandelion) have been found to be rich sources of polyphenols, including cinnamic acid derivatives, flavonoids and triterpenoids, which exert different biological activities, such as anti-inflammatory, anticancer and antimicrobial. Additionally, the whole plant is recognized as safe and well tolerated by humans, with no reported adverse effects. Nowadays, dandelion is a commonly available dietary supplement and a component of pharmaceutical preparations used for the treatment of bladder, liver, and spleen. Nevertheless, the effect of dandelion on blood platelets and plasma - components of hemostasis involved in the functioning of a cardiovascular system and linked with various cardiovascular diseases, has not been studied yet. Thus, the main objective of our in vitro experiments was to examine the anti-platelet and antioxidant properties of four standardized dandelion phenolic fractions, i.e. leaves 50% and 85% methanol fractions, and petals 50% and 85% methanol fractions, in blood platelets. Additionally, aforementioned plant preparations were investigated for hemostatic activity in plasma, using three selected hemostatic parameters: the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). None of the studied dandelion fractions, caused the damage of human blood platelets, at the whole tested range. The inhibition of lipid peroxidation in platelets treated with HO/Fe (the donor of OH) was observed for two fractions: leaves and petals 50% fractions, both at the dose 50 μg/mL. Analysis of the effect on the coagulation activity of human plasma demonstrated that three fractions: petals 50% fraction, and leaves and petals 85% fractions, significantly prolonged the thrombin time, at the whole tested range. On the contrary, none of the fractions changed the APTT andthe PT. The obtained results demonstrate that dandelion preparations, based on aerial parts, especially rich in hydroxycinnamic acid derivatives (leaves and petals 50% fractions) are promising plant materials exerting both antioxidant and anticoagulant activities of the hemostatic system that is beneficial in the prevention and treatment of cardiovascular diseases.

Food Res Int. 2018 May ;107:605-612. Epub 2018 Mar 5. PMID: 29580525

650
[+]

Neuroprotective effects of white tea against oxidative stress-induced toxicity in striatal cells.


Tea is one of the most widely consumed beverages in the world and represents an important source of antioxidants mainly catechins that confer beneficial effects in reducing the risk of cardiovascular diseases, age-related disorders or cancer. In the central nervous system, oxidative stress caused by increased production of reactive oxygen and nitrogen species represents an important mechanism for neuronal dysfunction and cell loss in different neurodegenerative disorders. The neuroprotective effects of green-tea-derived polyphenols have extensively been demonstrated in different models of neurotoxicity. However, few data have been reported on the antioxidant activity of white tea extracts in the nervous system. In the present study, we demonstrate that white tea extracts protect striatal cell lines against oxidative stress-mediated cell death. The effects of white tea on protection of striatal cell cultures are likely associated with the antioxidant properties of white tea components since neuronal cell loss induced by nonoxidative insults such as D1 dopamine receptor activation cannot be prevented by pre-treatment with white tea. Altogether our results suggest that regular consumption of white tea may contribute to reduce oxidative stress associated with brain injury and be clinically useful for treating age-related and neurodegenerative disorders.

Neurotox Res. 2011 Nov ;20(4):372-8. Epub 2011 Jun 23. PMID: 21698507

651
[+]

Caffeic acid versus caffeic acid phenethyl ester in the treatment of breast cancer MCF-7 Cells: migration rate inhibition.


Epithelium mammary carcinoma is a cancer with a high death rate among women. One factor having a significant impact on metastasis is cell migration. The aim of this study was to compare migration rate inhibition of caffeic acid (CA) and its phenethyl ester (CAPE) on MCF-7 breast cancer cells. Microscopic evaluation was used to determine the morphology of carcinoma cells, before and after 24-hour treatment with CA and CAPE using a dose of 50µM. The cytotoxic effect was measured by XTT-NR-SRB assay (tetrazolium hydroxide-neutral red-Sulforhodamine B) for 24-hour and 48-hour periods, using CA and CAPE, with doses of 50 and 100 µM. These doses were used to determine cell migration inhibition using a wound closure assay for 0-hour, 8-hour, 16-hour, and 24-hour periods. Both CA and CAPE treatments displayed cytotoxic activity in a dose- and time-dependent trend. CAPE displayed ICvalues more than twice as low as CA. ICvalues for the XTT assay were as follows: CA was 102.98µM for 24 hours and 59.12 µM for 48 hours, while CAPE was 56.39 µM for 24 hours and 28.10 µM for 48 hours. For the NR assay: CA was 84.87 µM at 24 hours and 65.05 µM at 48 hours, while CAPE was 69.05 µM at 24 hours and 29.05 µM at 48 hours. For the SRB assay: At 24 hours, CA was 83.47 µM and 53.46 µM at 48 hours, while CAPE was 38.53 µM at 24 hours and 20.15 µM at 48 hours. Both polyphenols induced migration inhibition, resulting in practically halting the wound closure. CAPE produced better results than CA with the same doses and experiment times, though both CA and CAPE displayedcytotoxic activity against MCF-7 cells, as well as inhibited migration.

Integr Cancer Ther. 2018 Sep 24:1534735418801521. Epub 2018 Sep 24. PMID: 30246565

652
[+]

Honokiol could counteract with cisplatin-induced damages in renal epithelial cells in vitro.


Cisplatin is a potent anti-cancer drug that has been widely used in the treatment of various cancers; however, cisplatin administration results in severe nephrotoxicity and impedes its clinical applications. In this study, we showed that honokiol, a polyphenol constituent extracted fromexhibited a short-term protective effect against cisplatin-induced damages in renal epithelial cells. The protective effects of honokiol were resulted from the combination of (1) reduced cellular oxidative stress ranging from 53 to 32% reduction during a 24-h incubation, (2) the maintenance of cellular antioxidant capacity and (3) the stabilization of cytoskeletal structure of the kidney epithelial cells. By promoting the polymerization of actin (1.6-fold increase) and tubulin (1.8-fold increase) cytoskeleton, honokiol not only maintained epithelial cell morphology, but also stabilized cellular localizations of tight junction protein Occludin and adhesion junction protein E-Cadherin. With stabilized junction protein complexes and structural polymerized cytoskeleton network, honokiol preserved epithelial cell polarity and morphology and thus reduced cisplatin-induced cell disruption and damages. Our data demonstrated for the first time that honokiol could counteract with cisplatin-induced damages in renal epithelial cells, futurestudies would further validate the potential clinical application of honokiol in cisplatin-based cancer treatments with reduced nephrotoxicity.

Front Pharmacol. 2018 ;9:357. Epub 2018 Apr 24. PMID: 29755347

653
[+]

Silibinin could be used to improve cancer therapeutics.


Silibinin is a natural plant polyphenol with high antioxidant and anticancer properties, which causes broad-spectrum efficacy against cancer, including cell cycle arrest and apoptosis in most cancer cell types. Silibinin, by modulating the apoptosis, cell cycle progression and autophagic pathways in various cellular and molecular routs might be used to design more effective anticancer strategies. Silibinin also regulates aberrant miRNAs expression linked to many aspects of cell biology in cancer. Maybe the most interesting aspect of silibinin is its ability to trigger multiple cellular signaling pathways to induce a particular biologic effect in various cell types. This review discusses investigations supporting the ability of silibinin to be as a natural modulator of involved cellular biological events in cancer progression. In this review, we introduce the salient features of silibinin therapy to optimize clinical outcomes for oncology patients. The goal of the treatments is to make it possible to eliminate the tumor with the minimum side effects and cure the patient in the early stage cancer. Therefore, plant extracts such as silibinin can be included in the treatments.

Life Sci. 2018 Oct 8. Epub 2018 Oct 8. PMID: 30308184

654
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The anthocyanins and polyphenols in blueberry are major functional ingredients for preventive chronic disease.


Functional ingredients in blueberry have the best health benefits. To obtain a better understanding of the health role of blueberry in chronic disease, we conducted systematic preventive strategies for functional ingredients in blueberry, based on comprehensive databases, especially PubMed, ISI Web of Science, and CNKI for the period 2008⁻2018. Blueberry is rich in flavonoids (mainly anthocyanidins), polyphenols (procyanidin), phenolic acids, pyruvic acid, chlorogenic acid, and others, which have anticancer, anti-obesity, prevent degenerative diseases, anti-inflammation, protective properties for vision and liver, prevent heart diseases, antidiabetes, improve brain function, protective lung properties, strong bones, enhance immunity, prevent cardiovascular diseases, and improve cognitive decline. The anthocyanins and polyphenols in blueberry are major functional ingredients for preventive chronic disease. These results support findings that blueberry may be one of the best functional fruits, and further reveals the mechanisms of anthocyanins and polyphenols in the health role of blueberry for chronic disease. This paper may be used as scientific evidence for developing functional foods, nutraceuticals, and novel drugsof blueberry for preventive chronic diseases.

Int J Mol Sci. 2018 Sep 16 ;19(9). Epub 2018 Sep 16. PMID: 30223619

655
[+]

Effect of xanthohumol and 8-prenylnaringenin on MCF-7 breast cancer cells oxidative stress and mitochondrial complexes expression.


Xanthohumol (XN) and 8-prenylnaringenin (8PN) are hop (Humulus lupulus L.) polyphenols studied for their chemopreventive effects on certain cancer types. The breast cancer line MCF-7 was treated with doses ranging from 0.001 to 20µM of XN or 8PN in order to assess the effects on cell viability and oxidative stress. Hoechst 33342 was used to measure cell viability and reactive oxygen species (ROS) production was determined by 2',7'-dichlorofluorescein diacetate. Catalase, superoxide dismutase, and glutathione reductase enzymatic activities were determined and protein expression of sirtuin1, sirtuin3, and oxidative phosphorylation system (OXPHOS) were done by Western blot. Treatments XN 0.01, 8PN 0.01, and 8PN 1 µM led to a decrease in ROS production along with an increase of OXPHOS and sirtuin expression; in contrast,XN 5 µM gave rise to an increase of ROS production accompanied by a decrease in OXPHOS and sirtuin expression. These results suggest that XN in low dose (0.01 µM) and 8PN at all assayed doses (0.001-20 µM) presumably improve mitochondrial function, whereas a high dose of XN (5 µM) worsens the functionality of this organelle.

J Cell Biochem. 2013 Dec ;114(12):2785-94. PMID: 23836544

656
[+]

Anticancer activity of calyx of Diospyros kaki Thunb.


BACKGROUND: Although it has been reported to contain high polyphenols, the pharmacological studies of the calyx of Diospyros kaki Thunb (DKC) have not been elucidated in detail. In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells.METHODS: Anti-cell proliferative effect of 70% ethanol extracts from the calyx of Diospyros kaki (DKC-E70) was evaluated by MTT assay. The effect of DKC-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively.RESULTS: DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β-catenin/TCF-dependent luciferase activity.CONCLUSIONS: Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

BMC Complement Altern Med. 2017 Sep 5 ;17(1):445. Epub 2017 Sep 5. PMID: 28870200

657
[+]

Carnosic acid regulates cell proliferation and invasion in chronic myeloid leukemia cancer cells.


PURPOSE: Carnosic acid (CA) is an important polyphenol mainly isolated from the famous spice and the medicinal plant Rosmarinus officinalis. CA has been shown to exhibit tremendous pharmacological properties which include, but are not limited to, anticancer, antioxidant and anti-inflammatory activities. The current study was designed to evaluate the anticancer effects of CA against chronic myeloid leukemia (CML) which is one of the rare but deadly malignancies both in men and women.METHODS: CML KBM-7 cell line was used in this study. Cell viability was assessed by MTT assay. Apoptosis was detected by DAPI and annexin V/PI staining, cell cycle analysis by flow cytometry and cell invasion by Boyden chamber assay. The microRNA-780 expression was determined by quantitative RT-PCR.RESULTS: Our results indicated that CA exhibits significant anticancer activity on CML KBM-7 cells with an IC50 of 25μM. The anticancer activity was due to induction of apoptosis and cell cycle arrest. Moreover, it was observed that CA inhibits the proliferation and invasion of CML KBM-7 cells which could mainly be due to downregulation of microRNA- 780 expression as indicated by the quantitative RT-PCR analysis.CONCLUSION: Taken together, we propose that carnosic acid could prove a potential lead compound in the treatment of CML and deserves further in vitro as well as in vivo study.

J BUON. 2018 May-Jun;23(3):741-746. PMID: 30003745

658
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Rosmarinic acid might be used as an adjuvant therapeutic factor in breast cancer treatment.


OBJECTIVES: Cancer is the second most common cause of death, with breast cancer (BC) as the most frequently diagnosed neoplasm among females. The origin of BC is multifactorial and depends on environmental and genetic factors. The disease presents a significant challenge due to its drug resistance and frequent metastasis. Thus, new effective therapies and metastasis prevention are much needed. Rosmarinic acid (RA) is a natural polyphenol which possesses the ability to inhibit BC cell proliferation and demonstrates cytotoxic properties against those cells. In our study, we examined the effect of RA on the expression of ZEB1, MDM2, ABCB1, PTEN and TWIST1 genes in MCF-7 breast cancer cells.MATERIAL AND METHODS: MCF-7 cell cultures were treated with 0.2μM doxorubicin (DOX) and 1.5, 15 or 50 μM of RA. Real-time PCR reaction was performed to analyze gene expression levels.RESULTS: PCR analysis showed a significant increase of the ZEB1 gene expression, which was about 3-fold for DOX 0.2μM, 9-fold for 0.2 μM DOX + 1.5 μM RA and 0.2 μM DOX + 15 μM RA (p

Ginekol Pol. 2018 ;89(10):541-545. PMID: 30393841

659
[+]

A review of the molecular targets of curcumin in breast cancer.


Curcumin (diferuloylmethane), an orange‑yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of Curcuma longa. For centuries, curcumin has been used in medicinal preparations and as a food colorant. In recent years, extensive in vitro and in vivo studies have suggested that curcuminpossesses activity against cancer, viral infection, arthritis, amyloid aggregation, oxidation and inflammation. Curcumin exerts anticancer effects primarily by activating apoptotic pathways in cancer cells and inhibiting pro‑cancer processes, including inflammation, angiogenesis and metastasis. Curcumin targets numerous signaling pathways associated with cancer therapy, including pathways mediated by p53, Ras, phosphatidylinositol‑3‑kinase, protein kinase B, Wnt‑β catenin and mammalian target of rapamycin. Clinical studies have demonstrated that curcumin alone or combined with otherdrugs exhibits promising anticancer activity in patients with breast cancer without adverse effects. In the present review, the chemistry and bioavailability of curcumin and its molecular targets in breast cancer are discussed. Future research directions are discussed to further understand this promising natural product.

Mol Med Rep. 2018 Nov 19. Epub 2018 Nov 19. PMID: 30483727

660
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Curcumin prevented human autocrine growth hormone signaling mediated NF-κB activation and miR-183-96-182 cluster stimulated EMT in T47D breast cancer cells.


Autocrine growth hormone (GH) signaling is a promoting factor for breast cancer via triggering abnormal cell growth, proliferation, and metastasis, drug resistance. Curcumin (diferuloylmethane), a polyphenol derived from turmeric (Curcuma longa), has anti-proliferative, anti-carcinogenic, anti-hormonal effect via acting on PI3K/Akt, NF-κB and JAK/STAT signaling. Forced GH expression induced epithelial mesenchymal transition (EMT) through stimulation of miR-182-96-183 cluster expression in breast cancer cells. This study aimed to investigate the role of NF-κB signaling and miR-182-96-183 cluster expression profile on autocrine GH-mediated curcumin resistance, which was prevented by time-dependent curcumin treatment in T47D breast cancer cells. Dose- and time-dependent effect of curcumin on T47D wt and GH+ breast cancer cells were evaluated by MTT cell viability and trypan blue assay. Apoptotic effect of curcumin was determined by PI and Annexin V/PI FACS flow analysis. Immunoblotting performed to investigate the effect of curcumin on PI3K/Akt/MAPK, NF-κB signaling. miR182-96-183 cluster expression profile was observed by qRT-PCR. Overexpression of GH triggered resistant profile against curcumin (20 µM) treatmentfor 24 h, but this resistance was accomplished following 48 h curcumin exposure. Concomitantly, forced GH induced invasion and metastasis through EMT and NF-κB activation were prevented by long-term curcumin exposure in T47D cells. Moreover, 48 h curcumin treatment prevented the autocrine GH-mediated miR-182-96-183 cluster expression stimulation in T47D cells. In consequence, curcumin treatment for 48 h, prevented autocrine GH-triggered invasion-metastasis, EMT activation through inhibiting NF-κB signaling and miR-182-96-183 cluster expression and induced apoptotic cell death by modulating Bcl-2 family members in T47D breast cancer cells.

Mol Biol Rep. 2018 Nov 23. Epub 2018 Nov 23. PMID: 30467667

661
[+]

Annurca apple polyphenols protect murine hair follicles from taxane induced dystrophy.


Chemotherapy-induced alopecia (CIA) is a common side effect of conventional chemotherapy and represents a major problem in clinical oncology. Even months after the end of chemotherapy, many cancer patients complain of hair loss, a condition that is psychologically difficult to manage. CIA disturbs social and sexual interactions and causes anxiety and depression. Synthetic drugs protecting from CIA and endowed with hair growth stimulatory properties are prescribed with caution by oncologists. Hormones, growth factors, morphogens could unwontedly protect tumour cells or induce cancer cell proliferation and are thus considered incompatible with many chemotherapy regimens. Nutraceuticals, on the contrary, have been shown to be safe and effective treatment options for hair loss. We here show that polyphenols fromcv Annurca are endowed with hair growth promoting activity and can be considered a safe alternative to avoid CIA. In vitro, Annurca Apple Polyphenolic Extract (AAE) protects murine Hair Follicles (HF) from taxanes induced dystrophy. Moreover, in virtue of its mechanism of action, AAE is herein proven to be compatible with chemotherapy regimens. AAE forces HFs to produce ATP using mitochondrialβ-oxidation, reducing Pentose Phosphate Pathway (PPP) rate and nucleotides production. As consequence, DNA replication and mitosis are not stimulated, while a pool of free amino acids usually involved in catabolic reactions are spared for keratin production. Moreover, measuring the effect exerted on Poly Unsaturated Fatty Acid (PUFA) metabolism, we prove that AAE promotes hair-growth by increasing the intracellular levels of Prostaglandins F2α (PGF2α) and by hijacking PUFA catabolites toward β-oxidation.

Nutrients. 2018 Nov 20 ;10(11). Epub 2018 Nov 20. PMID: 30463345

662
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The present review aims to offer a comprehensive perspective about the antitumour potential of the most promising compounds of walnut.


Even if cancer represents a burden for human society, an exhaustive cure has not been discovered yet. Low therapeutic index and resistance to pharmacotherapy are two of the major limits of antitumour treatments. Natural products represent an excellent library of bioactive molecules. Thus, tapping into the natural world may prove useful in identifying new therapeutic options with favourable pharmaco-toxicological profiles., or common walnut, is a very resilient tree that has inhabited our planet for thousands of years. Many studies correlate walnut consumption to beneficial effects towards several chronic diseases, such as cancer, mainly due to the bioactive molecules stored in different parts of the plant. Among others, polyphenols, quinones, proteins, and essential fatty acids contribute to its pharmacologic activity. The present review aims to offer a comprehensive perspective about the antitumour potential of the most promising compounds stored in this plant, such as juglanin, juglone, and the ellagitannin-metabolites urolithins or deriving from walnut dietary intake. All molecules and a chronic intake of the fruit provide tangible anticancer effects. However, the scarcity of studies on humans does not allow results to be conclusive.

Toxins (Basel). 2018 Nov 14 ;10(11). Epub 2018 Nov 14. PMID: 30441778

663
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Piceatannol can upregulate PI3K-Akt-eNOS signaling to protect cardiomyocytes from peroxidative injury.


Piceatannol (3,3',4,5'-trans-trihydroxystilbene) is a natural polyphenols compound that occurs hydroxylated analogue of resveratrol showing widely biological activities. Previous studies have demonstrated its functions on anti-cancer, neuroprotection and cardioprotection. However, few studies have clarified the benefits of piceatannol on cardiomyocytes except its anti-oxidative effect based on the original property of polyphenols. Here we apply H9c2 cardiomyocytes to study the cardioprotective mechanisms of piceatannol in vitro. We firstly verify its anti-peroxidation effect by using HO-induced in vitro model. Then, flow cytometry results show piceatannol reduce cellular apoptosis by enhancing Bcl-2 expressions in immunoblot analysis. Meantime, piceatannol decreases HO-induced excessive ROS and calcium overloading, and prevents mitochondrial depolarization. Most importantly, piceatannol pretreatment can regulate PI3K-Akt-eNOS signaling pathway to alleviate peroxidative injury. Immunoblot analysis of PI3K, Akt, p-Akt and eNOS shows HOsignificantly reduces expressions of these proteins. Pretreatment of piceatannol evidently increases their expressions and decreases iNOS expression, implying piceatannol can upregulate PI3K-Akt-eNOS signaling to protect cardiomyocytes from peroxidative injury.

Biomed Pharmacother. 2019 Jan ;109:886-891. Epub 2018 Nov 5. PMID: 30551542

664
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Sicilian litchi fruit extracts induce autophagy versus apoptosis switch in human colon cancer cells.


is a tropical tree whose fruits contain significant amounts of bioactive polyphenols. Litchi cultivation has recently spread in Sicily where the climate conditions are particularly favorable for this crop. Recent findings have shown that Litchi extracts display anti-tumor and pro-apoptotic effects in vitro, but the precise underlying mechanisms have not been fully elucidated. In this study, we report for the first time the effects of Sicilian litchi fruit extracts on colon cancer cells. The results indicated that litchi exocarp, mesocarp and endocarp fractions reduce the viability and clonogenic growth of HT29 cells. These effects were due to cell cycle arrest in the G2/M phase followed by caspase-dependent cell death. Interestingly, litchi exocarp and endocarp triggered a precocious autophagic response (16⁻24 h), which was accompanied by an increase in the level of autophagy related 1/autophagy activating kinase 1 (ATG1/ULK1), beclin-1, microtubule associated protein 1 light chain 3 (LC3)-II and p62 proteins. Autophagy inhibition by bafilomycin A1 or beclin-1 silencing increased cell death, thus suggesting that autophagy was initially triggered as a pro-survival response. Significant effects of Litchi extracts were also observed in other colon cancer cells, including HCT116 and Caco-2 cells. On the other hand, differentiated Caco-2 cells, a model of human enterocytes, appeared to be insensitive to the extracts at the same treatment conditions. High-Performance Liquid Chromatography⁻Electrospray Ionization-Quadrupole-Time-Of-Flight HPLC/ESI/Q-TOF evidenced the presence of some polyphenolic compounds, specifically in exocarp and endocarp extracts, that can account for the observed biological effects. The results obtained suggest a potential therapeutic efficacy of polyphenolic compounds purified from Sicilian Litchi fractions for the treatment of colon cancer. Moreover, our findings indicate that modulation of autophagy can represent a tool to improve the effectiveness of these agents and potentiate the anti-tumor response of colon cancer cells.

Nutrients. 2018 Oct 12 ;10(10). Epub 2018 Oct 12. PMID: 30322062

665
[+]

Carnosic acid enhances the anti-lung cancer effect of cisplatin.


Cisplatin and other platinum-based drugs are used frequently for treatment of lung cancer. However, their clinical performance are usually limited by drug resistance or toxic effects. Carnosic acid, a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), has been reported to have several pharmacological and biological activities. In the present study, the combination effect of cisplatin plus carnosic acid on mouse LLC (Lewis lung cancer) xenografts and possible underlying mechanism of action were examined. LLC-bearing mice were treated with intraperitoneal injection with cisplatin, oral gavage with carnosic acid, or combination with cisplatin and carnosic acid, respectively. Combination of carnosic acid and cisplatin yielded significantly better anti-growth and pro-apoptotic effects on LLC xenografts than drugs alone. Mechanistic study showed that carnosic acid treatment boosted the function of CD8T cells as evidenced by higher IFN-γ secretion and higher expression of FasL, perforin as well as granzyme B. In the meantime, the proportion of MDSC (myeloid-derived suppressor cells) in tumor tissues were reduced by carnosic acid treatment and the mRNA levels of iNOS2, Arg-1, and MMP9, which are the functional markers for MDSC, were reduced. In conclusion, our study proved that the functional suppression of MDSC by carnosic acid promoted the lethality of CD8T cells, which contributed to the enhancement of anti-lung cancer effect of cisplatin.

Chin J Nat Med. 2018 Dec ;16(12):907-915. PMID: 30595215

666
[+]

Emerging actions of pterostilebene on cancer research.


Pterostilbene (3,5-dimethoxy-4'-hydroxystilbene) is a polyphenolic compound primarily found in blueberries, grapes, and a tree wood, pterocarpus marsupium. Studies demonstrate that pterostilbene inhibits a variety of cancers, such as lung, breast, stomach, colon, etc. The anti-cancer activities are related to the regulation of several hallmarks of cancer. Moreover, pterostilbene exhibits much greater bioavailability and bioactivity than resveratrol which warrants further investigation in the anti-cancer functions and mechanisms.
.

Zhongguo Fei Ai Za Zhi. 2018 Dec 20 ;21(12):931-936. PMID: 30591102

667
[+]

Naringin acts as a chemosensitizer which synergistically strengthens the cytotoxic effect of paclitaxel in prostate cancer cells.


Background: The aim of the study was to evaluate whether the use of chemotherapy in combination with naringin, a dietary plant polyphenolic flavonoid, could enhance the therapeutic efficacy of paclitaxel treatment in human prostate cancer (PCa) cells. Materials and methods: DU145, PC3, and LNCaP cells were treated with various concentrations of paclitaxel, naringin, and their combinations. Methylthiazolyldiphenyl-tetrazolium bromide (MTT), image-based cytometer, quantitative reverse transcription PCR (RT-qPCR), Western blot, and transwell assay were used to evaluate cell viability, apoptosis and cell cycle, the mRNA expression, protein expression, and cell migration, respectively. Results: Naringin treatment inhibited cell survival in a dose- and time-dependent manner by inducing apoptosis and cell cycle arrest in G1 phase. Among the pathways evaluated, naringin (150 μM) significantly induced the mRNA expressions of,,,,,, and and downregulated the expressions of survivin and livin in DU145 cells. The combination of naringin and paclitaxel treatments synergistically increased the cytotoxic effects of paclitaxel in androgen-independent DU145 and PC3 cells, as well as in androgen-sensitive LNCaP cells. The combination ofnaringin with docetaxel has almost the same inhibitory effect on cell proliferation as the paclitaxel combination in androgen-independent cells, whereas there is no similar effect in LNCaP cells. Naringin exhibits significant inhibitory effects on the cell migration ability. The flavonoid either alone or in combination with paclitaxel therapy resulted in an increase in tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) protein expression and decrease in nuclear factor-κB p50 protein level in DU145 cells. Conclusion: In conclusion, naringin acts as a chemosensitizer which synergistically strengths the cytotoxic effect of paclitaxel in PCa cells. Therefore, naringin therapy alone or in combination with paclitaxel may be useful in the treatment of PCa. However, there is a need for more detailedstudies of the mechanism of action.

Prostate Int. 2018 Dec ;6(4):126-135. Epub 2017 Nov 28. PMID: 30505814

668
[+]

Crocetin and crocin from saffron in cancer chemotherapy and chemoprevention.


Since ancient times herbs and spices have been used with strong roles on cultural heritage and on the appreciation of food and its links to health. Today, an important element of chemoprevention drug development is the new approach that uses specific natural products or plant's derivatives to suppress, reverse or prevent cell premalignant transformation in malignant form. It is also very important to note that suitable chemoprevention natural agents should have low or no toxicity, high efficacy, should be orally administrable, to have a known mechanism of action and low cost compared to the other chemotherapeutic agents. Natural products are composed of a wide spectrum of biologically active phytochemicals as polyphenols, flavonoids, carotenoids, alkaloid, and so on. Preclinical studies showed that carotenoids have potent antitumor effects both in vitro and in vivo, suggesting potential preventive and/or therapeutic roles. The potential cancer protective effect of carotenoids has been extensively studied mainly in relation to their antioxidant properties, but carotenoids (β-carotene, lycopene, lutein and zeaxantin, crocin and crocetin) have several other biological activities which involve multiple mechanisms promoting the inhibition of malignant tumor growth and the induction of apoptosis. Saffron, the dry stigmas of the Crocus sativus L., is an important source ofcarotenoids and has been used in traditional medicine in various parts of the world. The present review provides an updated overview of experimental in vitro and in vivo investigations on the potential use of saffron's carotenoids: crocin and crocetin in cancer therapy and chemoprevention trials.

Anticancer Agents Med Chem. 2018 Dec 30. Epub 2018 Dec 30. PMID: 30599111

669
[+]

These results showed that oleuropein is a potential therapeutic and preventive agent for breast cancer.


Breast cancer is the most common malignancy in the world with the highest rate of morbidity and mortality. Due to the several side effects of chemotherapy and radiotherapy, recent studies have focused on the use of herbal medicines. Epidemiological reports have shown the inverse relationship between breast cancer risk and intake of olive. Oleuropein (OLE) is a polyphenolic compound in virgin olive oil with antineoplastic properties and it is well tolerated by humans. Recent reports have shown that OLE has effects on the control of cancer by modulating epigenetics, such as histone deacetylase (HDAC) inhibition. However, the epigenetic mechanisms of OLE anticancer properties are yet to be properly investigated. Therefore, this study aimed to determine the therapeutic effects of OLE through the modulation of histone deacetylase 2 (HDAC2) and histone deacetylase 3 (HDAC3) expression in breast cancer cell line. MCF-7 cells were tested with and without OLE, and also the cell viability, apoptosis, and migration were examined. HDAC2 and HDAC3 expression genes were assessed by quantitative real-time polymerase chain reaction. It was found that OLE decreased the expression of both HDAC2 and HDAC3 (P 

J Cell Biochem. 2019 Jan 7. Epub 2019 Jan 7. PMID: 30618185

670
[+]

This review sheds light on the molecular targets of phloretin as a potential anti-cancer and anti-inflammatory natural agent.


Apple is a rich source of bioactive phytochemicals that help improve health by preventing and/or curing many disease processes, including cancer. One of the apple polyphenols is phloretin [2',4',6'-Trihydroxy-3-(4-hydroxyphenyl)-propiophenone], which has been widely investigated for its antioxidant, anti-inflammatory and anti-cancer activities in a wide array of preclinical studies. The efficacy of phloretin in suppressing xenograft tumor growth in athymic nude mice implanted with a variety of human cancer cells, and the ability of the compound to interfere with cancer cells signaling, have made it a promising candidate for anti-cancer drug development. Mechanistically, phloretin has been reported to arrest the growth of tumor cells by blocking cyclins and cyclin-dependent kinases and induce apoptosis by activating mitochondria-mediated cell death. The blockade of the glycolytic pathway via downregulation of GLUT2 mRNA and proteins, and the inhibition of tumor cells migration, also corroborates the anti-cancer effects of phloretin. This review sheds light on the molecular targets of phloretin as a potential anti-cancer and anti-inflammatory natural agent.

Molecules. 2019 Jan 13 ;24(2). Epub 2019 Jan 13. PMID: 30642127

671
[+]

Theaflavin-3,3'-digallate might be used as an adjuvant to potentiate the inhibitory effect of cisplatin against advanced ovarian cancer.


Ovarian cancer has the highest fatality rate among the gynecologic cancers. The side effects, high relapse rate, and drug resistance lead to low long-term survival rate (less than 40%) of patients with advanced ovarian cancer. Theaflavin-3,3'-digallate (TF3), a black tea polyphenol, showed less cytotoxicity to normal ovarian cells than ovarian cancer cells. We aimed to investigate whether TF3 could potentiate the inhibitory effect of cisplatin against human ovarian cancer cell lines. In the present study, combined treatment with TF3 and cisplatin showed a synergistic cytotoxicity against A2780/CP70 and OVCAR3 cells. Treatment with TF3 could increase the intracellular accumulation of platinum (Pt) and DNA-Pt adducts and enhanced DNA damage induced by cisplatin in both cells. Treatment with TF3 decreased the glutathione (GSH) levels and upregulated the protein levels of the copper transporter 1 (CTR1) in both cells, which led to the enhanced sensitivity of both ovarian cancer cells to cisplatin. The results imply that TF3 might be used as an adjuvant to potentiate the inhibitory effect of cisplatin against advanced ovarian cancer.

Int J Mol Sci. 2018 Jan 2 ;19(1). Epub 2018 Jan 2. PMID: 29301278

672
[+]

Myricetin inhibits panel of kinases implicated in tumorigenesis.


About 80% of the antineoplastic drugs produced in the last 30 years are of natural origin or their derivatives, evidencing the great contribution of natural products in the development of new drugs (1). Phytochemical constituents of various plants are a source of biomolecules candidates (2), including polyphenols as flavonoids, showing expressive antioxidant (3, 4) and anticancer features (5). Flavonoids constituents are known for their antitumour activity such as inhibition of cell proliferation, adhesion and invasion, cell cycle arrest and apoptosis (6). This article is protected by copyright. All rights reserved.

Basic Clin Pharmacol Toxicol. 2019 Jan 9. Epub 2019 Jan 9. PMID: 30624861

673
[+]

Diosmin induces genotoxicity and apoptosis in DU145 prostate cancer cell line.


Plant-derived dietary polyphenolic compounds, such as flavonoids, with cancer cell-specific pro-apoptotic activity and chemopreventive potential are thought to be promising anticancer agents. In the present study, we were interested in determining if flavonoid-induced genotoxicity may also provoke cancer cell death. Cyto- and genotoxicity of three selected flavonoid glycosides (naringin, diosmin and hesperidin) in DU145 prostate cancer cell line were investigated. Flavonoid glycosides decreased cancer cell number and proliferative activity in a different manner. Flavonoid glycosides induced oxidative stress: intracellular total ROS and superoxide production were augmented after flavonoid treatment. Flavonoid glycosides stimulated DNA double strand breaks (DSBs) and micronuclei production. Diosmin was found the most potent genotoxic agent in DU145 cells, which, in turn, resulted in its pro-apoptotic activity. The more robust recruitment of 53BP1 was correlated with lower DNA and chromosomal damage after naringin and hesperidin treatment compared with diosmin treatment. Flavonoid glycosides were also found to be DNA hypomethylating agents with an ability to modulate cancer cell epigenome leading to changes in the gene expression patterns. Taken together, diosmin, a dietary flavonoid glycoside, was found active against DU145 cells by promoting genotoxic events and a concomitant apoptotic cell death. Thus, a comprehensive analysis of biological activity of diosmin against cancer cells both in vitro and in vivo deserves further investigation.

Toxicol In Vitro. 2015 Apr ;29(3):417-25. Epub 2014 Dec 11. PMID: 25499067

674
[+]

Antioxidant and anticancer activities of chamomile.


OBJECTIVES: The present study aimed at determining the antioxidant activity, total phenols and flavonoids and to evaluate the antiproliferative activity of ethanolic extract of Matricaria recutita L. (chamomile). The antioxidant activities were measured using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. The total phenolic content was measured by the Folin-Ciocalteu assay. The flavonoid content was determined using the aluminum chloride method. The MTT assay was used to estimate the antiproliferative activities against human hepatoma (HepG2) cancer cell line. We assessed the mode of action of the extract as a cancer preventive agent and reported its ability to regulate tumor angiogenesis by down regulating in a dose dependent manner the expression of some proteins involved in the process.RESULTS: The percentage inhibition of DPPH scavenging activity was dose-dependent ranging between (94.8% ± 0.03) at 1.50 mg/mL and (84.2% ± 0.86) at 0.15 mg/mL. It showed high polyphenols (21.4 ± 0.327 mg GAE/g) and high flavonoids content (157.9 ± 2.22 mg QE/g). Effect of extract was investigated against HepG2 cells. A dose-dependent reduction in cell viability was recorded incells treated with the extract. The ICwas ~ 300 µg/mL. It significantly inhibited the level of important prerequisite angiogenesis markers both in HepG2 cells and ex vivo.

BMC Res Notes. 2019 Jan 3 ;12(1):3. Epub 2019 Jan 3. PMID: 30602390

675
[+]

Molecular mechanisms underlying curcumin-mediated therapeutic effects in type 2 diabetes and cancer.


The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-known polyphenol derived from the rhizomes of turmeric, has attracted a great deal of attention as a natural compound with beneficial antidiabetic and anticancer properties, partly due to its antioxidative and anti-inflammatory actions. Although this polyphenolic compound is increasingly being recognized for its growing number of protective health effects, the precise molecular mechanisms through which it reduces diabetes- and cancer-related pathological events have not been fully unraveled. Hence, CUR is the subject of intensive research in the fields Diabetology and Oncology as a potential candidate in the treatment of both T2DM and cancer, particularly since current therapeutic options for their treatment are not satisfactory in clinics. In this review, we summarize the recent progress made on the molecular targets and pathways involved in antidiabetic and anticancer activities of CUR that are responsible for its beneficial health effects.

Oxid Med Cell Longev. 2018 ;2018:9698258. Epub 2018 Mar 20. PMID: 29743988

676
[+]

Urolithin A gains in antiproliferative capacity by reducing the glycolytic potential via the p53/TIGAR axis in colon cancer cells.


Polyphenols have shown promising bioactivity in experimental in vitro and in vivo models for cancer chemoprevention. However, consumed orally, they are often transformed by gut microbes into new active principles with so far incompletely deciphered molecular mechanisms. Here, enterolacton, S-equol and urolithin A as representatives of metabolites of lignans, isoflavones and ellagitannins, respectively, were examined for their impact on HCT116 colon cancer cell growth, cooperativity with oxaliplatin and p53 dependency in vitro. Whereas enterolacton and S-equol (≤60 µM) did not elicit growth inhibition or positive cooperativity with oxaliplatin, urolithin A showed an IC50 value of 19 µM (72 h) and synergism with oxaliplatin. Urolithin A induced p53 stabilization and p53 target gene expression, and absence of p53 significantly dampened the antiproliferative effect of urolithin A (IC50(p53-/-) = 38 µM). P53 was dispensable for the G2/M arrest in HCT116 cells but required for induction of a senescence-like phenotype upon long-term exposure and for the observed synergism with oxaliplatin. Moreover, extracellular flux analyses and knockdown approachesuncovered a reduced glycolytic potential via the p53/TIGAR axis which was linked to the higher susceptibility of wildtype cells to urolithin A. Overall, the p53 status turned out to be an important determinant for the potential benefit of dietary ellagitannins in cancer chemoprevention or use in adjuvant therapy.

Carcinogenesis. 2019 Mar 12 ;40(1):93-101. PMID: 30418550

677
[+]

Aspalathin reverts doxorubicin-induced cardiotoxicity.


Doxorubicin (Dox) is an effective chemotherapeutic agent used in the treatment of various cancers. Its clinical use is often limited due to its potentially fatal cardiotoxic side effect. Increasing evidence indicates that tumour protein p53 (p53), adenosine monophosphate-activated protein kinase (AMPK), nucleoporin p62 (p62), and the mammalian target of rapamycin (mTOR) are critical mediators of Dox-induced apoptosis, and subsequent dysregulation of autophagy. Aspalathin, a polyphenolic dihydrochalcone-glucoside has been shown to activate AMPK while decreasing the expression of p53. However, the role that aspalathin could play in the inhibition of Dox-induced cardiotoxicity through increased autophagy flux remained unexplored. H9c2 cardiomyocytes and Caov-3 ovarian cancer cells were cultured in Dulbecco's Modified Eagle's medium and treated with or without Dox for five days. Thereafter, cells exposed to 0.2µM Dox were co-treated with either 20 µM Dexrazozane (Dexra) or 0.2 µM aspalathin (ASP) daily for 5 days. Results obtained showed that ASP mediates its cytoprotective effect in a p53-dependent manner, by increasing the Bcl-2/Bax ratio and decreasing apoptosis. The latter effect was diminished through ASP-induced activation of autophagy-related genes (Atgs) with an associated decrease in p62 through induction of AMPK and Fox01. Furthermore, we showed that ASP was able to potentiate this effect without decreasing the anti-cancer efficacy of Dox, as could be observed in Caov-3 ovarian cancer cells. Taken together, the data presented in this study provides a credible mechanism by which ASP co-treatment could protect the myocardium from Dox-induced cardiotoxicity.

Molecules. 2017 Sep 22 ;22(10). Epub 2017 Sep 22. PMID: 28937626

678
[+]

Epigallocatechin-3-gallate (EGCG) induces telomere shortening and clastogenic damage in glioblastoma cells.


Epigallocatechingallate (EGCG) is the major polyphenol in green tea, to which many anticancer features, such as anti-oxidative, anti-genotoxic and anti-angiogenetic properties, are attributed. Moreover, it is also well known as a telomerase inhibitor. In this work, we have chronically treated U251 glioblastoma cells with low, physiologically realistic concentrations, of EGCG, in order to investigate its effects both on telomeres and on genome integrity. Inhibition of telomerase activity caused telomere shortening, ultimately leading to senescence and telomere dysfunction at 98 days. Remarkably, we have observed DNA damage through an increase of phosphorylation ofγ-H2AX histone and micronuclei also with doses and at timepoints when telomere shortening was not present. Therefore, we concluded that this DNA damage was not correlated with telomere shortening and that EGCG treatment induced not only an increase of telomere-shortening-induced senescence, but also telomere-independent genotoxicity. This study questions the common knowledge about EGCG properties, but confirms the few works that indicated the clastogenic properties of this molecule, probably due to DNA reductive damage and topoisomerase II poisoning.

Environ Mol Mutagen. 2019 Apr 26. Epub 2019 Apr 26. PMID: 31026358

679
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Epigallocatechin-3-gallate inhibits doxorubicin-induced inflammation on human ovarian tissue.


Chemotherapy protocol can destroy the reproductive potential of young cancer patients. Doxorubicin (DOX) is a potent anthracycline commonly used in the treatment of numerous malignancies. The purpose of the study was to evaluate the ovarian toxicity of DOX via inflammation and the possible protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG). Ovarian tissue of three patients was cultured with 1µg/ml DOX and/or 10µg/ml EGCG for 24 and 48 hours. Levels of inflammatory factors were determined by western blot, zimography, quantitative Real-Time PCR and multiplex bead-based immunoassay. Morphological evaluation, damaged follicle count and TUNEL assay were also performed. DOX influenced inflammatory responses by inducing a significant increase in the expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and cyclooxigenase-2 (COX-2), of inflammatory interleukins, such as interleukin-6 (IL-6) and interleukin-8 (IL-8), and the inflammatory proteins mediators metalloproteinase-2 and metalloproteinase-9 (MMP2 and MMP9). IL-8 secretion in the culture supernatants and MMP9 activity also significantly raised after DOX treatment. Moreover, a histological evaluation of the ovarian tissue showed morphological damage to follicles and stroma after DOX exposure. EGCG significantly reduced DOX-induced inflammatory responses and improved the preservation of follicles.: DOX-induced inflammation could be responsible for the ovarian function impairment of chemotherapy. EGCG could have a protective role in reducing DOX-mediated inflammatory responses in human ovarian tissue.

Biosci Rep. 2019 Apr 17. Epub 2019 Apr 17. PMID: 30996116

680
[+]

The obtained data suggest an anticancer effect of oleuropein, alone and in combination with 2-methoxyestradiol.


BACKGROUND/AIM: Oleuropein belongs to the potent polyphenols of olive oil. Notably, it is considered as a potentially active anticancer agent. Herein, the anticancer efficiency of oleuropein, when used separately and in combination with the chemotherapeutic agent, 2-methoxyestradiol (2-ME), was investigated in highly metastatic osteosarcoma (OS) cells.MATERIALS AND METHODS: Human OS cells (143B OS cell line) were incubated with oleuropein and 2-ME, alone or in combination. Cell viability was determined by the MTT assay. Cell migration assays were used in order to determine the anti-migratory potential of the compounds, while their impact on autophagy was evaluated via the LC3-antibody-based detection assay. The interaction between oleuropein and 2-ME was determined via the CalcuSyn software.RESULTS: Both anti-migratory and anti-proliferative effects of oleuropein were demonstrated on human OS cells. Anticancer effects of oleuropein were significantly enhanced after 2-ME addition. Treatment of 143B OS cell with oleuropein, alone or in combination with 2-ME resulted in induction of autophagy.CONCLUSION: The obtained data suggest an anticancer effect of oleuropein, alone and in combination with 2-ME, on highly metastatic 143B OS cells. Notably, a synergism between oleuropein and 2-ME towards 143B OS cells was detected. The exact mechanism of this synergism needs to be further investigated; nonetheless, induction of nitro-oxidative stress and/or induction of autophagy are suggested.

Anticancer Res. 2019 Mar ;39(3):1243-1251. PMID: 30842154

681
[+]

This review summarizes the potential anti-aging effects of hydroxytyrosol and its protective role in several age-related diseases.


Aging is a complex process. It is considered a risk factor for several diseases such as cancer, neurodegenerative diseases, cardiovascular diseases, and diabetes, most of which have an oxidative and inflammatory base. Given that life expectancy is increasing, there is a present interest in the search for anti-aging strategies that allow a healthy aging. Interestingly, in Spain, where the Mediterranean Diet (MD) is the reference food pattern, life expectancy will have the highest average by 2040. This diet is characterized, among other items, by virgin olive oil intake, which contains between 50-200 mg/kg of hydroxytyrosol, a major polyphenolic component of olive oil. Hydroxytyrosol is formed by the hydrolysis of oleuropein during the maturing of olives, storage of olive oil, and preparation of table olives. It is a yield of oleuropein by microbiota action in the organism after virgin oliveoil consumption. The daily intake in context of the MD is estimated to be around 0.15 and 30 mg/day. In the last few years, hydroxytyrosol has received increasing attention due to its multiple pharmacological activities, such as antioxidant, anti-inflammatory and pro-apoptotic activities. It has also been the focus of extensive research regarding its bioactivity. In this sense, hydroxytyrosol is under consideration for the development of new anti-aging strategies. In this review we will summarize the potential anti-aging effects of hydroxytyrosol and its protective role in several age-related diseases.

Pharmacol Res. 2019 May ;143:58-72. Epub 2019 Mar 7. PMID: 30853597

682
[+]

Oleuropein exhibits an anti-cancer effect by modulation of tumor suppressor gene expression, which is targeted by oncomiRs.


Breast cancer (BC) is the leading cause of cancer mortality in women worldwide. It recently was proven that miRNAs play a critical role in BC development. The use of natural agents for control of cancer by modulating miRNAs is promising. Oleuropein is a natural polyphenolic agent with anti-neoplastic properties and is well tolerated by humans. This study was undertaken to determine the therapeutic effects of oleuropein through modulation of master oncomiRs (miR-21 and miR-155) in BC cells. The present study provides the first link between miRNA and oleuropein as a mechanism in BC. MCF-7 cells were tested with and without oleuropein and the cell viability, apoptosis, and migration were examined. The effect of oleuropein on miR-21 and miR-155 expression was assessed through qRT-PCR. It was found that oleuropein induced apoptosis and retarded cell migration and invasion in a dose-dependent manner in the human MCF7 BC cell line. It was observed that oleuropein significantly decreased expression of both miR-21 and miR-155 over time in a dose-dependent manner. These results demonstrate that oleuropein is a potential therapeutic and preventive agent for BC. Oleuropein exhibits an anti-cancer effect by modulation of tumor suppressor gene expression, which is targeted by oncomiRs.

J Cell Biochem. 2018 Sep ;119(9):7151-7165. Epub 2018 Jun 15. PMID: 29905007

683
[+]

Anticancer activity of methanol extract of Ficus carica leaves and fruits against proliferation, apoptosis, and necrosis in Huh7it cells.


The polyphenol plant extracts have previously been demonstrated to act as chemopreventive and anticancer agents.is a rich source of polyphenols, yet its antioxidant and anticancer activities remain poorly characterized. This study aimed to determine the anticancer activity ofleaf and fruit extracts by investigating their impact on proliferation, apoptosis, and Huh7it cell necrosis. Leaves and fruits were extracted using methanol, and the phytochemical contents were analyzed using Fourier-transform infrared spectroscopy. The antioxidant activity was measured using the 2,2-diphenyl-1-picrylhydrazyl method. Anticancer activities were examined through MTT (3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay on Huh7it liver cancer cells. The apoptosis and necrosis conditions were examined using Annexin biomarkers V-PI and later analyzed in flow cytometry.leaves and fruit examined were found to have strong antioxidant activities with ICvalues of 7.9875µg/mL and 13.402 µg/mL, respectively. MTT assay results indicatedleaves and fruit had ICvalues>653μg/mL and>2000μg/mL, respectively. The flow cytometry analysis indicated a higher percentage of Huh7it apoptosis and necrosis in leaf extracts compared with fruit extracts. The difference in anticancer activity was attributed to differing compounds present in each extract.

Cancer Inform. 2019 ;18:1176935119842576. Epub 2019 Apr 19. PMID: 31037025

684
[+]

Chlorogenic acid inhibits osteosarcoma carcinogenesis via suppressing the STAT3/Snail pathway.


Chlorogenic acid (CA) is a polyphenol compound that possesses anticancer effects on several types of tumors. However, there are few previous studies concerning the protective effects of CA on osteosarcoma. The current study aimed to examine the toxicity of CA to osteosarcoma cells and to explore the potential mechanisms. Cell growth was evaluated using cell counting kit-8 assay and Western blot analysis of proliferating cell nuclear antigen (PCNA). Apoptosis was assessed by flow cytometry analysis using flow cytometry and caspase-3/7 activity assay. The expression changes of the signal transducer and activator of transcription 3 (STAT3)/Snail pathway were detected by Western blot analysis. We found that CA dose-dependently inhibited cell viability and PCNA expression in osteosarcoma cells. Meanwhile, CA treatment increased the apoptotic rate and caspase-3/7 activity in osteosarcoma cells in a concentration-dependent manner. We found that CA concentration-dependently inhibited the activation of the STAT3/Snail pathway in osteosarcoma cells. Inhibition of the STAT3/Snail pathway by si-STAT3 retarded the growth and induced apoptosis of osteosarcoma cells. Mechanistically, activation of the STAT3/Snail pathway by pcDNA-STAT3 reversed the effects of CA on osteosarcoma cell growth and apoptosis. In conclusion, CA inhibited osteosarcoma carcinogenesis by suppressing osteosarcoma cell growth and inducing apoptosis, which was involved in inactivation of the STAT3/Snail pathway. Therefore, our study suggested that CA might have good therapy prospects in osteosarcoma therapy.

J Cell Biochem. 2019 Jun ;120(6):10342-10350. Epub 2018 Dec 23. PMID: 30582213

685
[+]

Chlorogenic acid may act as a chemosensitizing agent leading to cancer growth suppression.


New paradigm in cancer pathogenesis revealed that microenvironmental conditions significantly contribute to cancer. Hence, Warburg stated that cancer is a metabolic disease. Chlorogenic acid (CGA) is a polyphenol that is found abundantly in coffee. This compound has proven ability in ameliorating some metabolic diseases through various pathways. This article will elaborate the potency of CGA as a chemosensitizer in suppressing tumor growth through a metabolic pathway. AMPK pathway is the main cell metabolic pathway that is activated by CGA in some studies. Moreover, CGA inhibited EGFR/PI3K/mTOR, HIF, VEGF pathways and MAPK/ERK pathway that may suppress tumor cell growth. Furthermore, CGA induced intracellular DNA damage and topoisomerase I- and II-DNA complexes formation that plays a key role in apoptosis. Conclusively, based on the ability of CGA in activate and inhibit some important pathways in cancer metabolism, it may act as a chemosensitizing agent leading to cancer growth suppression.

J Evid Based Integr Med. 2018 Jan-Dec;23:2515690X18789628. PMID: 30051721

686
[+]

Chlorogenic acid improves the regorafenib effects in human hepatocellular carcinoma cells.


Chlorogenic acid (CGA) is a polyphenol present in many human dietary foods. Several studies indicated a beneficial role of CGA in the prevention of cancer and an enhancement of chemotherapy when combined with CGA in the treatment of human hepatocarcinoma (HCC). Drug toxicity, resistance and subsequent disease progression represent a problem in HCC management, although treatment with the multikinase inhibitor Regorafenib improved overall survival. This study focused on the evaluation of the effects of combined treatment using both low Regorafenib concentrations and CGA as natural compound in HCC cells. The analysis of cell proliferation by Ki67 staining and cell cycle progression showed that CGA enhanced Regorafenib-mediated cell growth inhibition. Moreover, CGA potentiated the apoptotic effect of Regorafenib by the activation of the pro-apoptotic Annexin V, Bax and Caspase 3/7 and the inhibition of anti-apoptotic Bcl2 and Bcl-xL. Combined treatments were also effective in inhibiting cell motility. The mechanisms underlying the positive effects of combining CGA and Regorafenib were also addressed and an increased inhibition of MAPK (mitogen-activated protein kinase)and PI3K/Akt/mTORC (phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling was observed. Overall, these data demonstrated that co-treatment with Regorafenib and CGA enhanced Regorafenib action, reducing its cytotoxicity in HCC cells. In conclusion, this drug combination could be considered as a safe and more effective approach in HCC therapy.

Int J Mol Sci. 2018 May 19 ;19(5). Epub 2018 May 19. PMID: 29783729

687
[+]

Protective effect of Fisetin against angiotensin II-induced apoptosis.


BACKGROUND: Fisetin, a polyphenolic compound, has drawn notable attention owing to its antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. However, the cardiac effects of fisetin are not clear yet.HYPOTHESIS: The aim of the present study is to examine the cardioprotective effect of fisetin against Ang-II induced apoptosis in H9c2 cells and in spontaneous hypertensive rats (SHR).METHODS/STUDY DESIGN: The in vitro protective effect of fisetin was evaluated after the cells were treated with fisetin (50 µM/ml/ 24  h) for 2  h prior or after Ang-II administration to induce apoptosis. For in vivo experiments, SHRs were orally administered with fisetin (10  mg/kg) twice a week for 6 weeks. Cellular apoptosis was analyzed by TUNEL staining assay and the modulation in the expression levels of proteins involved in apoptosis and cell survival were determined by western blotting.RESULTS: Our results demonstrate the potent cardioprotective efficacy of fisetin against Ang-II induced apoptosis in H9c2 cells and in SHR models. Fisetin administration reduced the apoptotic nuclei considerably And reduced the expression of apoptotic proteins such as TNF-α, Fas L, FADD, Cleaved caspase-3 and Cleaved PARP and increased the cell survival and anti-apoptotic proteins like Bcl-2, Bcl-xp-IGF1R, p-PI3K and p-AKT in both in vitro and in vivo models.CONCLUSION: In conclusion, the results of the present study reveal that fisetin activates the IGF-IR-dependent p-PI3K/p-Akt survival signaling pathway and suppresses the caspase dependent apoptosis.

Phytomedicine. 2019 Apr ;57:1-8. Epub 2018 Sep 17. PMID: 30668312

688
[+]

Fisetin suppresses migration, invasion and stem-cell-like phenotype of human non-small cell lung carcinoma cells.


Fisetin (3,3',4',7-tetrahydroxyflavone) is a bioactive polyphenolic flavonoid found in many fruits and vegetables. It exhibits a variety of pharmacological activities including anticancer and anti-invasive effects. Epithelial to mesenchymal transition (EMT) allows the tumor cells to acquire increased migratory and invasive properties mediating their dissemination to faraway sites, thus favoring metastasis. With metastatic lung cancer claiming the majority of lung cancer-related deaths, agents targeting the pathways underlying metastasis are translationally promising. In the present study, we have explored the anti-metastatic effects of fisetin in non-small cell lung carcinoma (NSCLC) cells A549 and H1299 with emphasis on EMT. The results suggested a significant inhibition in migration and invasion of NSCLC cells under non-cytotoxic concentrations. Furthermore, an attenuation of the EMT was observed in both the cell lines with upregulation in the expression of epithelial marker E-cadherin in A549 cells and ZO-1 in H1299 cells with concomitant downregulation of the mesenchymal markers vimentin as well as N-cadherin along with invasion marker MMP-2. Herein, the downregulation of the expression of NSCLC stem cell signature markers CD44 and CD133 was also observed. Fisetin decreased the expression of multiple signaling proteins (β-catenin, NF-κB, EGFR, STAT-3) acting upstream to EMT and known to be involved in induction and maintenance of mesenchymal phenotype, which may explain the observed effects. Moreover, fisetin decreased the ability of H1299 cells to form colonies on soft agar and potentiated the cytotoxic effects of tyrosine kinase inhibitor (TKI), erlotinib. Overall, our study suggested the ability of fisetin to serve as a potential therapeutic agent on its capacity to attenuate the EMT program and inhibit migration, invasion and stem cell phenotype of lung cancer cells.

Chem Biol Interact. 2019 Apr 25 ;303:14-21. Epub 2019 Feb 22. PMID: 30802432

689
[+]

Flaxseed lignans as important dietary polyphenols for cancer prevention and treatment.


Cancer causes considerable morbidity and mortality across the world. Socioeconomic, environmental, and lifestyle factors contribute to the increasing cancer prevalence, bespeaking a need for effective prevention and treatment strategies. Phytochemicals like plant polyphenols are generally considered to have anticancer, anti-inflammatory, antiviral, antimicrobial, and immunomodulatory effects, which explain their promotion for human health. The past several decades have contributed to a growing evidence base in the literature that demonstrate ability of polyphenols to modulate multiple targets of carcinogenesis linking models of cancer characteristics (i.e., hallmarks and nutraceutical-based targeting of cancer) via direct or indirect interaction or modulation of cellular and molecular targets. This evidence is particularly relevant for the lignans, an ubiquitous, important class of dietary polyphenols present in high levels in food sources such as flaxseed. Literature evidence on lignans suggests potential benefit in cancer prevention and treatment. This review summarizes the relevant chemical and pharmacokinetic properties of dietary polyphenols and specifically focuses on the biological targets of flaxseed lignans. The consolidation of the considerable body of data on the diverse targets of the lignans will aid continued research into their potential for use in combination with other cancer chemotherapies, utilizing flaxseed lignan-enriched natural products.

Pharmaceuticals (Basel). 2019 May 5 ;12(2). Epub 2019 May 5. PMID: 31060335

690
[+]

Effect of yellowing time on bioactive compounds in yellow tea and their antiproliferative capacity in HepG2 cells.


Several studies have shown potent antineoplastic effects of tea, which can induce apoptosis and inhibit proliferation of cancer cells. Yellow tea is one of the six major types of tea, and yellowing time, a key factor in its processing, is known to improve its quality and bioactivity. However, the effects of yellowing on the composition of the bioactive substances of tea are poorly understood. We analyzed the biochemical composition and the antioxidant and anticancer activities of the extracts of yellow tea (EYTs) subjected to different yellowing durations. Prolonged yellowing increased the content of water extracts, amino acids, soluble sugars, theaflavins, and nonesterified catechins (0.05, 

Food Sci Nutr. 2019 May ;7(5):1838-1847. Epub 2019 Apr 18. PMID: 31139398

691
[+]

Oleuropein has the potential to be a therapeutic drug for breast cancer prevention and treatment.


Breast cancer (BC) is one of the most common cancers among women worldwide. Genetic, epigenetic, and environmental factors play a crucial role in BC development. Because epigenetic imbalance occurs earlier than expression in carcinogenesis and is reversible, epigenetic reprogramming strategies could be more useful for cancer prevention and therapy. There is evidence indicating that the use of herbal compounds with low toxicity can offer a real benefit in the prevention or treatment of cancer. Oleuropein (OLE), as a natural polyphenol, has shown the anticancer property in cancers. In this study, we investigated for the first timethe link between histone deacetylase (HDAC) and OLE to have an anticancer effect in BC. The potential apoptotic and anti-invasive effects of OLE were tested using MCF-7 cells. Transcript expression of HDAC1 and HDAC4 genes after treatment was determined using quantitative reverse transcription polymerase chain reaction. OLE obviously reduced invasiveness and cell viability and simultaneously induced cell apoptosis in MCF-7 cancer cells. Dose-dependent reduction of HDAC4 was observed, whereas apparent changes could not be observed in HDAC1 expression. The current research indicated that OLE can inhibit proliferation and invasion of cells by inducing apoptosis likely through modulation of an important epigenetic factor, HDAC4, in MCF-7 cells. OLE has the potential to be a therapeutic drug for BC prevention and treatment.

J Cell Biochem. 2019 May 22. Epub 2019 May 22. PMID: 31119806

692
[+]

An olive leaf extract rich in polyphenols promotes apoptosis in cervical cancer cells.


Most of the common drugs used to treat the cervical cancer, which main etiological factor is the HPV infection, cause side effects and intrinsic/acquired resistance to chemotherapy. In this study we investigated whether an olive leaf extract (OLE), rich in polyphenols, was able to exert anti-tumor effects in human cervical cancer cells (HeLa). MTT assay results showed a reduction of HeLa cells viability OLE-induced, concomitantly with a gene and protein down-regulation of Cyclin-D1 and an up-regulation of p21, triggering intrinsic apoptosis. OLE reduced NFkB nuclear translocation, which constitutive activation, stimulated by HPV-oncoproteins, promotes cancer progression and functional studies revealed that OLE activated p21in a transcriptional-dependent-manner, by reducing the nuclear recruitment of NFkB on its responsive elements. Furthermore, OLE treatment counteracted epithelial-to-mesenchymal-transition and inhibited anchorage-dependent and -independent cell growth EGF-induced. Finally, MTT assay results revealed that OLE plus Cisplatin strengthened the reduction of cells viability Cisplatin-induced, as OLE inhibited NFkB, AkT and MAPK pathways, all involved in Cisplatin chemoresistance. In conclusion, we demonstrated that in HeLa cells OLE exerts pro-apoptotic effects, elucidating the molecular mechanism and that OLE could mitigate Cisplatin chemoresistance. Further studies are needed to explore the potential coadiuvant use of OLE for cervical cancer treatment.

Nutr Cancer. 2019 ;71(2):320-333. Epub 2019 Jan 19. PMID: 30661406

693
[+]

This study highlights the promising use of curcumin as a chemosensitizer in the treatment of breast cancer.


Doxorubicin is one of the most widely used chemotherapy agents for the treatment of breast cancer. However, the development of doxorubicin resistance limits the long‑term treatment benefits in patients with breast cancer. Curcumin, a well‑known dietary polyphenol derived from the rhizomes of turmeric (Curcuma longa), enhances the sensitivity of breast cancer cells to chemotherapeutic agents; however, the mechanisms underlying this phenomenon remain unclear. The aim of the present study was to evaluate the effect of curcumin on chemoresistance in doxorubicin‑resistant breast cancerMCF‑7/DOX and MDA‑MB‑231/DOX cell lines. Cell Counting Kit‑8, monolayer transport, western blot and ATPase activity assays were performed during the study. The results revealed that curcumin significantly enhanced the effect of doxorubicin in doxorubicin‑resistant breast cancer cells. The intracellular accumulation of doxorubicin was substantially increased following curcumin treatment in doxorubicin‑resistant breast cancer cells, in a manner that was inversely dependent on the activity of ATP binding cassette subfamily B member 4 (ABCB4). Treatment with a combination of curcumin and doxorubicin decreases the efflux of doxorubicin in ABCB4‑overexpressing cells. Furthermore, curcumin inhibited the ATPase activity of ABCB4 without altering its protein expression. In conclusion, curcumin reversed doxorubicin resistance in human breast cancer MCF‑7/DOX and MDA‑MB‑231/DOX cells by inhibiting the ATPase activity of ABCB4. The study highlights the promising use of curcumin as a chemosensitizer in the treatment of breast cancer.

Mol Med Rep. 2019 Jun ;19(6):5162-5168. Epub 2019 Apr 22. PMID: 31059026

694
[+]

EGCG may be considered a novel anti-cervical cancer drug in the future.


The aim of the present study was to investigate the inhibitory effects of the polyphenol epigallocatechin-3-gallate (EGCG) on the growth of cervical carcinoma cell lines infected with different high-risk human papillomavirus (HPV) subtypes, as well as the associated regulation of microRNA (miR) expression. Cell proliferation was measured using an MTT assay. The effects of 7 different concentrations of EGCG (100, 80, 60, 40, 20, 10 and 0µg/ml) on HeLa cell proliferation were assessed. HeLa cell growth was significantly inhibited by EGCG in a dose- and time-dependent manner (P

Exp Ther Med. 2019 Mar ;17(3):1742-1748. Epub 2018 Dec 24. PMID: 30783443

695
[+]

Deciphering the nutraceutical potential of Raphanus sativus-A comprehensive overview.


(Radish) belongs to the Brassicaceae family and is a widely consumed root vegetable all around the world. The nutritional and medicinal values of radishes have been proven by several researches. Extracts prepared from the aerial and underground parts of radishes have been used in the treatment of stomach disorders, urinary infections, hepatic inflammation, cardiac disorders and ulcers in folk medicine since the ancient times. The pharmaceutical potential of radishes is attributed to the presence of its beneficial secondary metabolites, such as glucosinolates, polyphenols and isothiocyanates. The present review has focused on the impact of radish extract administration under pathological complications, such as cancer, diabetes, hepatic inflammation and oxidative stress. In addition, a comprehensive view of molecular mechanism behind the regulation of molecular drug targets associated with different types of cancers and diabetes by the bioactive compounds present in the radish extracts have been discussed in detail.

Nutrients. 2019 Feb 14 ;11(2). Epub 2019 Feb 14. PMID: 30769862

696
[+]

Chemopreventive effects of strawberry and black raspberry on colorectal cancer in inflammatory bowel disease.


Colorectal cancer (CRC) remains the third most common cause of cancer-related death in the United States and the fourth globally with a rising incidence. Inflammatory bowel disease (IBD) is a chronic immunologically mediated disease that imposes a significant associated health burden, including the increased risk for colonic dysplasia and CRC. Carcinogenesis has been attributed to chronic inflammation and associated with oxidative stress, genomic instability, and immune effectors as well as the cytokine dysregulation and activation of the nuclear factor kappa B (NFκB) signaling pathway. Current anti-inflammation therapies used for IBD treatment have shown limited effects on CRC chemoprevention, and their long-term toxicity has limited their clinical application. However, natural food-based prevention approaches may offer significant cancer prevention effectswith very low toxicity profiles. In particular, in preclinical and clinical pilot studies, strawberry and black raspberry have been widely selected as food-based interventions because of their potent preventive activities. In this review, we summarize the roles of strawberry, black raspberry, and their polyphenol components on CRC chemoprevention in IBD.

Nutrients. 2019 Jun 3 ;11(6). Epub 2019 Jun 3. PMID: 31163684

697
[+]

In vitro antioxidant and cancer inhibitory activity of a colored avocado seed extract.


Avocado () seeds have been used traditionally for a number of health-related indications. Because of its high polyphenol content, we investigated the potential antioxidant and anticancer effects of a colored avocado seed extract (CASE). CASE exhibited an oxygen radical acceptance capacity value of 2012± 300 trolox equivalents/mg. CASE reduced lipid hydroperoxide formation in an oil-in-water emulsion (33% reduction at 500g/mL). CASE dose-dependently reduced the viability of human breast (MCF7), lung (H1299), colon (HT29), and prostate (LNCaP) cancer cells. The half maximal inhibitory concentrations ranged from 19 to 132g/mL after treatment for 48 h. CASE treatment downregulated the expression of cyclin Dand Ein LNCaP cells. This was associated with cell G/Gphase cycle arrest. CASE also dose-dependently induced apoptosis in LNCaP cells. CASE reduced nuclear translocation of nuclear factorB, a prosurvival signal. Further studies are needed to examine these effects inmodels.

Int J Food Sci. 2019 ;2019:6509421. Epub 2019 Apr 24. PMID: 31179313

698
[+]

Urolithin A induces prostate cancer cell death in p53-dependent and in p53-independent manner.


PURPOSE: Pomegranate and walnuts are widely consumed dietary sources and contain several bioactive compounds, including the ellagitannins (ETs). ETs are polyphenols that are metabolized in the gut microbiota to urolithin A (UA). p53 is a tumor suppressor that lost its activity through MDM2 activation in about half cancers. The purpose of this study was to investigate the influence of UA on the p53-MDM2 interaction pathway in prostate cancer cell lines.METHODS: Three human prostate cancer cell lines were used that harbor different p53 genotypes; LNCaP (p53), 22RV1(p53) and PC3 (p53). Cell viability was determined by CellTiter-Glo Luminescent assay. Apoptosis was confirmed by measuring annexin V by flow cytometry. The expression of p53, its target proteins, and apoptotic markers were measured by western blotting. Real-time qPCR was used to measure the gene expression of p21, a main target gene of p53. Co-immunoprecipitation-immunoblotting was used to assess the inhibition of interactions between p53 and MDM2 and to assess the effect of UA on MDM2-mediated p53 polyubiquitination.RESULTS: We found UA inhibited CaP cells' viability and induced apoptosis. For 22RV1 and LNCaP, we found UA increased p53 protein expression and its main target protein, p21, and MDM2, forming an autoregulatory feedback loop. In addition, UA increased the p53 proapoptotic proteins PUMA and NOXA. Moreover, UA inhibited the interaction between p53 and MDM2 and inhibited MDM2-mediated p53 polyubiquitination. UA downregulated MDM2 and XIAP protein expression in PC3 cells and upregulated p21 and p14ARF in a p53-independent manner.CONCLUSION: The influencing of UA on p53-MDM2 pathway may partly contribute to its anticancer effect.

Eur J Nutr. 2019 Jun 8. Epub 2019 Jun 8. PMID: 31177307

699
[+]

Morin protects human respiratory cells from fine particulate matter induced genotoxicity.


Chronic fine particulate matter (PM) exposure causes oxidative stress and leads to many diseases in human like respiratory and cardiovascular disorders, and lung cancer. It is known that toxic responses elicited by PMparticles depend on its physical and chemical characteristics that are greatly influenced by the source. Dietary polyphenolic compounds that possess antioxidant and free radical scavenging properties could be used for therapeutic or preventive approaches against air pollution related health hazards. This study evaluates characteristics and toxicity of PMcollected from rural, urban, industrial, and traffic regions in and around Coimbatore City, Tamilnadu, India. Traffic PMparticles contained higher amounts of metals and polycyclic aromatic hydrocarbons (PAHs). It also possessed higher levels of oxidative potential, induced more intracellular reactive oxygen species (ROS), and caused more levels of cell death and DNA damage in human respiratory cells. Its exposure up regulated DNA damage response related miR222, miR210, miR101, miR34a, and miR93 and MycN and suppressed Rad52. Pre-treatment with morin significantly decreased the PMinduced toxicity and conferred protection against PMinduced altered miRNA expression. Results of this study showed that cytoprotective effect of morin is due to its antioxidative and free radical scavenging activity.

Int J Environ Res Public Health. 2019 Jul 5 ;16(13). Epub 2019 Jul 5. PMID: 31284452

700
[+]

Curcumin-loaded mesoporous silica nanoparticles markedly enhanced cytotoxicity in hepatocellular carcinoma cells.


Curcumin, a natural polyphenol extracted from a perennial herbhas been verified for many physiological activities such as anti-oxidant, anti-inflammatory, and anti-tumor properties. The direct use of curcumin cytotoxicity studies are limited due to its unstable chemical structure, low bioavailability, easy oxidation, and degradation by ultraviolet (UV) light etc. Trying to overcome this problem, silica-encapsulated curcumin nanoparticles (SCNP) and chitosan with silica co-encapsulated curcumin nanoparticles (CSCNP) were prepared by silicification and biosilicification methods, respectively, and encapsulated curcumin within it. We investigated the antitumor properties of SCNP and CSCNP on different tumor cell lines. Scanning electron microscopy (SEM) analysis revealed that both SCNP and CSCNP were almost spherical in shape and the average particle size of CSCNP was 75.0± 14.62 nm, and SCNP was 61.7 ± 23.04 nm. The results show that CSCNP has more anti-oxidant activity as compared to curcumin and SCNP. The higher cytotoxicity towards different cancerous cell lines was also observed in CSCNP treated tumor cells. It was noted that the SCNP and CSCNP has a high percentage of ICvalues in Hep G2 cells. The encapsulation of curcumin improved instability, antioxidant activity, and antitumor activity. Our results demonstrated that nanoencapsulation of curcumin with silica and chitosan not only increase curcumin stability but also enhance its cytotoxic activity on hepatocellular carcinoma cells. On the basis of these primary studies, the curcumin-loaded nanoparticles appear to be promising as an innovative therapeutic material for the treatment of tumors.

Int J Mol Sci. 2019 Jun 14 ;20(12). Epub 2019 Jun 14. PMID: 31207976

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