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

701
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The role of polyphenol compounds in the treatment of cancer cells.


Cancer remains a second leading cause of deaths and major public health problem. It occurs due to extensive DNA damage caused by ultraviolet radiations, ionizing radiations, environmental agents, therapeutic agents, etc. Among all cancers, the most frequently diagnosed cancers are lung (12.7%), breast (10.9%), colorectal (9.7%), and gastric cancer (7.81%). Natural compounds are most favorable against cancer on the count of their anti-cancerous ability, easy to avail and efficient. Among natural compounds, polyphenols (flavonoids, catechin, hesperetin, flavones, quercetin, phenolic acids, ellagic acid, lignans, stilbenes, etc.) represent a large and diverse group used in the prevention and treatment of cancer. Natural flavonoids are derived from different plant sources and from various medicinal plants including,,,, etc. Natural flavonoids possess antioxidant, anti-inflammation, as well as anti-cancerous activities through multiple pathways, they induce apoptosis in breast, colorectal, and prostate cancers, lower the nucleoside diphosphate kinase-B activity in lung, bladder and colon cancers, inhibit cell-proliferation and cell cycle arrest by suppressing the NF-kB pathway in various cancers, etc. The current review summarized the anticancer activities of natural polyphenols and their mechanisms of action. Abbreviations Akt pathway A Serine/Threonine-Protein Kinase pathway COX-2 Cyclooxygenase-2 HaCaT Cultured Human Keratinocyte HDAC Histone Deacetylase MAPK pathway Mitogen-Activated Protein Kinases pathway (Oestrogen Receptor); NF-kBkappa-light-chain-enhancer of activated B cell PARP Poly ADP Ribose Polymerase ROS Reactive oxygen Speciese STAT-1 Signal Transducer and Activator of Transcription 1.

Nutr Cancer. 2019 Jul 9:1-12. Epub 2019 Jul 9. PMID: 31287738

702
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Apigenin may inhibit colorectal cancer cell growth and progression through induction of apoptosis rather than cell necrosis or senescence.


INTRODUCTION: Deregulation of Thyroid Hormones (THs) system in Colorectal Cancer (CRC) suggests that these hormones may play roles in CRC pathogenesis. Flavonoids are polyphenolic compounds, which possess potent antitumor activities and interfere, albeit some of them, with all aspects of THs physiology. Whether the antitumor actions of flavonoids are affected by THs is unknown. Therefore, we investigated the effects of Apigenin (Api), a well-known flavone, on some tumorigenic properties of SW480 CRC cells in the presence and absence of L-thyroxine (T4).METHODS: Cell viability was assessed by MTT assay. Flow cytometry and DNA electrophoresis were used to evaluate cell death. Cell senescence was examined by in situ detection ofβ-galactosidase activity. Protein expression was assessed by antibody array technique.RESULTS: While T4 had minimal effects, Api reduced cell growth and senescence by induction of apoptosis. Expression of anti-apoptotic and pro-apoptotic proteins were differentially affected by Api and T4. Survivin, HSP60 and HTRA were the most expressed proteins by the cells. Almost all Api-induced effects persisted in the presence of T4.CONCLUSION: These data suggest that Api may inhibit CRC cell growth and progression through induction of apoptosis rather than cell necrosis or senescence. In addition, they suggest that T4 has minimal effects on CRC cell growth, and is not able to antagonize the anti-growth effects of Api. Regardless of the treatments, cells expressed high levels of survivin, HSP60 and HTRA, indicating that these proteins may play central roles in SW480 CRC cell immortality.

Anticancer Agents Med Chem. 2019 07 3. Epub 2019 Jul 3. PMID: 31272364

703
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Therapeutic promises of Chlorogenic acid with special emphasis on its anti-obesity property.


BACKGROUND: Chlorogenic acid (CGA) is a quinic acid conjugate of caffeic acid. It is an ester formed between caffeic acid and the 3-hydroxyl of L-quinic acid. This polyphenol is naturally present in substantial amount in the green coffee beans. Minor quantities of CGA are also reported in apples, eggplant, blueberries, tomatoes, strawberries and potatoes. CGA is reported to be beneficial in hypertension, hyperglycemia, antimicrobial, antitumor, memory enhancer, weight management etc. Further, it is also reported to have anticancer, antioxidant and anti-inflammatory activities. Since last decade, CGA drew public attention for its widely recommended use as medicine or natural food additive supplement for the management of obesity.OBJECTIVE: The current review explores the medicinal promises of CGA and emphasizes on its anti-obese property as reported by various scientific reports and publication.CONCLUSION: CGA shows promises as an antioxidant, glycemic control agent, anti-hypertensive, anti-inflammatory, antimicrobial, neuro-protective and anti-obesity agent. It primarily activates the AMP-activated protein kinase, inhibits 3-hydroxy 3-methylglutaryl coenzyme-A reductase and strengthens the activity of carnitine palmitoyltransferase to control the obesity.

Curr Mol Pharmacol. 2019 Jul 16. Epub 2019 Jul 16. PMID: 31333144

704
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Lonicera japonica Thunb. Induces caspase-dependent apoptosis through death receptors and suppression of AKT in U937 human leukemic cells.


Decoctions obtained from the dried flowers of Lonicera japonica Thunb. (Indongcho) have been utilized in folk remedies against inflammatory diseases. Recently, many agents that have used for inflammatory diseases are showing anticancer effects. Here, we have isolated polyphenols extracted from lyophilized Lonicera japonica Thunb (PELJ) and investigated the anticancer effects of PELJ on U937 cells. Here, we demonstrated that PELJ induced apoptosis by upregulation of DR4 and Fas, and further it is augmented by suppression of XIAP. In addition, The PELJ-induced apoptosis is at least in part by blocking PI3K/Akt pathway. These findings suggest that PELJ may provide evidence of anticancer activities on U937 cells. Further study for detailed mechanism and the effects on animal models is warranted to determine whether PELJ provide more conclusive evidence that PELJ which may provide a beneficial effect for treating cancer.

Phytother Res. 2018 Mar ;32(3):504-513. Epub 2017 Nov 29. PMID: 29193390

705
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Polyphenolic compounds from Korean Lonicera japonica Thunb. induces apoptosis via AKT and caspase cascade activation in A549 cells.


Thunb. (T.) has historically been used in Korean herbal medicine due to its anticancer and protective effects on the respiratory system. In the present study, the polyphenolic compounds inT. were investigated using high-performance liquid chromatography coupled with tandem mass spectrometry, and its anticancer effects on A549 non-small-cell lung cancer cells were studied. Polyphenolic compounds potentially inhibit A549 cells in a dose-dependent manner. Flow cytometry and western blot analysis demonstrated that polyphenolic compounds induce apoptosis by regulating the protein expression levels of caspases, poly-(ADP-ribose) polymerase and the B-cell lymphoma-2-associated X-protein/B-cell lymphoma-extra large ratio. Furthermore, polyphenolic compounds inhibited mitochondrial membrane potential activity. Caspase-3 activity was increased in a dose-dependent manner and polyphenolic compounds inhibited the activation of protein kinase B by dephosphorylation. These results suggest that polyphenolic compounds in A549 cells indicate the anticancer activity through the induction of apoptosis.

Oncol Lett. 2017 Apr ;13(4):2521-2530. Epub 2017 Feb 23. PMID: 28454429

706
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Polyphenolic extract isolated from Korean Lonicera japonica Thunb. induce G2/M cell cycle arrest and apoptosis in HepG2 cells.


Lonicera japonica Thunb. (L. japonica T.) has been used in Korean traditional medicine for long time because of its anti-cancer and hepatic protective effect. In this study, we investigated polyphenolic extract in L. japonica T. using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) and its anti-cancer effect on hepatocarcinoma cells. Human HepG2 cell line was treated with various concentrations of polyphenolic extract. Apoptosis was detective by cell morphology, cell cycle analysis and immunoblot analysis. Polyphenolic extract inhibited cell proliferation at 48h in a dose-dependent manner. Polyphenolic extract affected HepG2 cell viability by inhibiting cell cycle progression at the G2/M transition and inducing apoptosis. Polyphenolic extract also decreased the expression of CDK1, CDC25C, cyclin B1, pro-caspases-3 and -9 and poly ADP ribose polymerase, and affected the levels of mitochondrial apoptotic-related proteins. The phosphorylation of extracellular signal-related kinase½ (ERK 1/2), c-Jun N-terminal kinase (JNK), and p-38 mitogen-activated protein kinases (MAPKs) were increased in HepG2 cells treated with polyphenolic extract, whereas Akt was dephosphorylated. These results indicate that inhibition of PI3K/Akt and activation of MAPKs are pivotal in G2/M cell cyclearrest and apoptosis of human hepatocarcinoma cells mediated by polyphenolic extract.

Food Chem Toxicol. 2012 Jul ;50(7):2407-16. Epub 2012 Apr 27. PMID: 22561682

707
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Phenolic profile of edible honeysuckle berries (genus lonicera) and their biological effects.


The current status of research on polyphenolic compounds in the berries of edible honeysuckle and their biological effects, including recommended utilization, are reviewed. The major classes of phenolic compounds in the blue berried honeysuckle are flavonols (quercetin, rutin, quercitrin) and flavanes (proanthocyanidins, catechins) and anthocyanins. Cyanidin-3-glucoside and cyanidin-3-rutinoside are considered as major anthocyanidins in edible honeysuckle berries. Such a high level of antioxidant activity in the berries of different species of the genus Lonicera is especially due to the high level of polyphenolic compounds, especially anthocyanins. These berries seem to be prospective sources of health-supporting phytochemicals that exhibit beneficial anti-adherence and chemo-protective activities, thus they may provide protection against a number of chronic conditions, e.g., cancer, diabetes mellitus, tumour growth or cardiovascular and neurodegenerative diseases.

Molecules. 2011 Dec 22 ;17(1):61-79. Epub 2011 Dec 22. PMID: 22269864

708
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A diet including beans might represent health benefits and cancer-preventive effects.


Two varieties of common beans (Phaseolus vulgaris L.), Bayo Victoria and Negro 8025, were evaluated to determine the effect on cellular viability and mechanisms involved in apoptosis pathways, using a cellular model with HT-29 cells. Aqueous methanolic (50:50) extracts from cooked beans were analyzed for phenolic composition, identifying greater diversity of phenolic compounds in Bayo Victoria extracts. However, Negro 8025 showed greater phenolic content and cytotoxicity effects at lower media inhibitory concentrations, and greater effectiveness to activate apoptotic pathways. Proteins related to the arrest of cell cycle were modulated by both bean cultivars. Qualitative analysis by HPLC-PAD and HPLC-MS systems of phenolic compounds in common bean extracts showed mainly hydroxybenzoic and hydroxycinnamic acids, flavonols, and monomeric flavan-3-ols. Bioactive phenolics such as catechin, kaempferol, and ferulic acid were found in both cultivars as well anticancer phytochemicals such as quercetin, protocatechuic acid, myricetin, naringenin and their derivatives, and procyanidins. PRACTICAL APPLICATIONS: Polyphenols in common beans (Phaseolus vulgaris L.) cultivars processed by canning display chemoprotective potential as they activate mechanisms involved in apoptosis pathways. Phenolics in common beans modulate 28 proteins related to apoptotic processes. Therefore, a diet including canned beans (particularly darker varieties) might represent health benefits and cancer-preventive effects.

J Food Biochem. 2019 Jun ;43(6):e12680. Epub 2018 Sep 16. PMID: 31353616

709
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Resveratrol is a promising agent for colorectal cancer prevention and treatment.


Colorectal cancer (CRC) is the third most common cancer and one of the main causes of cancer death entire the world. Environmental, dietary, and lifestyle factors including red meat consumption, cigarette smoking, alcohol intake and family history are the most important risk factors of CRC. Multiple pathways including inflammation, oxidative stress, and apoptosis are involved in its incidence and progression. Resveratrol, a polyphenolic compound, has different pharmacologic functions including anti-inflammation, cancer prevention, lipid-lowering effect, and hypoglycemic effect. Many studies have proved that resveratrol might also represent a chemo preventive effect on CRC. Thus, the aim of the current review is to depict the role of resveratrol in treatment of CRC in a molecular manner.

Cancer Cell Int. 2019 ;19:180. Epub 2019 Jul 15. PMID: 31341423

710
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The current review summarizes the existing in vitro and in vivo animal and human studies examining the nephroprotective effects of resveratrol.


Different diseases and disorders that affect the kidneys include, but are not limited to, glomerulonephritis, diabetic nephropathy, polycystic kidney disease, kidney stones, renal fibrosis, sepsis, and renal cell carcinoma. Kidney disease tends to develop over many years, making it difficult to identify until much later when kidney function is severely impaired and undergoing kidney failure. Although conservative care, symptom management, medication, dialysis, transplantation, and aggressive renal cancer therapy are some of the current strategies/approaches to kidney disease treatment, new preventative targeted therapies are needed. Epidemiological studies have suggested that a diet rich in fruits and vegetables is associated with health benefits including protection against kidney disease and renal cancer. Resveratrol, a polyphenol found in grapes and berries, has been reported to have antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, and anti-cancer properties. The current review summarizes the existing in vitro and in vivo animal and human studies examining the nephroprotective effects of resveratrol.

Nutrients. 2019 Jul 17 ;11(7). Epub 2019 Jul 17. PMID: 31319485

711
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Pro-apoptotic effect of grape seed extract on MCF-7 cells.


Growing evidence suggests dietary antioxidants reduce the risk of several cancers. Grape seeds extracts (GSE) are a rich source of polyphenols known to have antioxidant, chemopreventive and anticancer properties. Herein, we investigated the in vitro effects and putative action mechanisms of a grape seed extract (GSE) on human breast cancer cells (MCF-7). The effects of GSE were evaluated on cell proliferation, apoptosis and gap-junction-mediated cell-cell communications (GJIC), as basal mechanism involved in the promotion stage of carcinogenesis. GSE (0.05-100μg/mL) caused a significant dose- and time-dependent inhibition of MCF-7 viability and induced apoptotic cell death, as detected by Annexin-V/Propidium Iodide. Concurrently, GSE induced transient but significant enhancement of GJIC in non-communicating MCF-7 cells, as demonstrated by the scrape-loading/dye-transfer (SL/DT) assay and an early and dose-dependent re-localization of the connexin-43 (Cx43) proteins on plasma membranes, as assayed by immunocytochemistry. Finally, real-time-PCR has evidenced a significant increase inmRNA expression. The results support the hypothesis that the proliferation inhibition and pro-apoptotic effect of GSE against this breast cancer cell model are mediated by the GJIC improvement via re-localization of Cx43 proteins and up-regulation ofgene, and provide further insight into the action mechanisms underlying the health-promoting action of dietary components.

Int J Mol Sci. 2019 Jul 2 ;20(13). Epub 2019 Jul 2. PMID: 31269652

712
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Antioxidant, antimicrobial, and antiproliferative activity-based comparative study of peel and flesh polyphenols from Actinidia chinensis.


Background: Kiwifruit () peel has been always considered as useless because of the harsh taste. To promote the full utilization of kiwifruit resources it is essential to explore the nutritional benefits of kiwifruit peel.Objective: Our studies explored the difference in polyphenolic composition and biological activity including antioxidant, antimicrobial, and antiproliferative activity of the flesh and peel of kiwifruit.Design: Antioxidant activity of the extracted polyphenols of the peel and flesh ofwas checked by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis3-ethylbenzothiazoline-6-sulphonic acid (ABTS), hydroxyl ion reduction, and ion chelating ability. Antibacterial activity against,, andand antiproliferative activityHepG2 was tested in a dose- and time-dependent manner. Liquid chromatography/mass spectrometry (LC/MS) chromatogram of the peel and flesh further differentiated the phenolic acid profile.Results: The pericarp of kiwifruit was found to be more abundant in polyphenols and flavonoids than the flesh, with contents of 12.8 mg/g and 2.7 mg/g, respectively. LC/MS analysis revealed that the catachin, quercetin and epigallocatechin content (the main polyphenols in kiwifruit) in the peel was significantly higher than in the flesh (

Food Nutr Res. 2019 ;63. Epub 2019 Apr 26. PMID: 31073285

713
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Anticancerous effect of rutin against HPV- C33A cervical cancer cells via G0/G1 cell cycle arrest and apoptotic induction.


BACKGROUND: Nowadays the potential therapeutic role of various bioflavonoids including Curcumin, Luteolin and Resveratrol has currently been well-documented in a vast range of fatal complications including synaptic failure and cancers. These bioflavonoids are widely being implemented in the treatment of various cancers as these possess anti-cancerous, anti-oxidant and anti-inflammatory properties. Moreover, these are also used as a better alternative to conventional therapies since; these are non-toxic to cells and having no or least side effects. Notably, the pertinent therapeutic role of Rutin in cervical cancer is still unsettled however its anti-cancerous role has already been reported in other cancers including prostate and colon cancer. Rutin (Vitamin P or Rutoside) is a polyphenolics flavonoid exhibiting multi-beneficial roles against several carcinomas.OBJECTIVE: Despite the evidence for its several biological activities, the anticancer effects of Rutin on human cervical cancer (C33A) cells remain to be explored. In this study, the anticancer potential of Rutin was investigated by employing the key biomarkers such as nuclear condensation reactive oxygen species (ROS), apoptosis, and changes in mitochondrial membrane potential (MMP).RESULTS: Our findings showed that Rutin treatment reduced the cell viability, induced significant increase in ROS production and nuclear condensation in dose dependent manner. Moreover, Rutin provoked apoptosis by inducing decrease in MMP and activation of caspase-3. Cell cycle analysis further confirmed the efficacy of Rutin by showing cell cycle arrest at G0/G1 phase.CONCLUSION: Thus, our study is envisaged to open up interests for elucidating Rutin as an anti-cancerous agent against cervical cancer.

Endocr Metab Immune Disord Drug Targets. 2019 Aug 6. Epub 2019 Aug 6. PMID: 31385777

714
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Curcumin binds to α-Syn Oligomers and reduces their toxicity.


In human beings, Parkinson's disease (PD) is associated with the oligomerization and amyloid formation ofα-synuclein (α-Syn). The polyphenolic Asian food ingredient curcumin has proven to be effective against a wide range of human diseases including cancers and neurological disorders. While curcumin has been shown to significantly reduce cell toxicity of α-Syn aggregates, its mechanism of action remains unexplored. Here, using a series of biophysical techniques, we demonstrate that curcumin reduces toxicity by binding to preformed oligomers and fibrils and altering their hydrophobic surface exposure. Further, our fluorescence and two-dimensional nuclear magnetic resonance (2D-NMR) data indicate that curcumin does not bind to monomeric α-Syn but binds specifically to oligomeric intermediates. The degree of curcumin binding correlates with the extent of α-Syn oligomerization, suggesting that the ordered structure of protein is required for effective curcumin binding. The acceleration ofaggregation by curcumin may decrease the population of toxic oligomeric intermediates of α-Syn. Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases.

ACS Chem Neurosci. 2013 Mar 20 ;4(3):393-407. Epub 2012 Dec 17. PMID: 23509976

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