Cancer Metastasis https://greenmedinfo.com/taxonomy/term/5092/all en Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells. https://greenmedinfo.com/article/nobiletin-attenuates-metastasis-both-erk-and-pi3kakt-pathways-hgf-treated-live PMID:  Phytomedicine. 2013 Jun 15 ;20(8-9):743-52. Epub 2013 Mar 26. PMID: 23537747 Abstract Title:  Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells. Abstract:  Hepatocyte growth factor (HGF), and its receptor, c-Met activation has recently been shown to play important roles in cancer invasion and metastasis in a wide variety of tumor cells. We use HGF as an invasive inducer of human HepG2 cells to investigate the effect of four flavones including apigenin, tricetin, tangeretin, and nobiletin on HGF/c-Met-mediated tumor invasion and metastasis. Among them, nobiletin markedly inhibited HGF-induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and transwell-chamber invasion/migration assay under non-cytotoxic concentrations. Data also showed nobiletin inhibited HGF-induced cell scattering and cytoskeleton changed such as filopodia and lamellipodia. Furthermore, nobiletin could inhibit HGF-induced the membrane localization of phosphorylated c-Met, ERK2, and Akt, but not phosphorylated JNK1/2 and p38. Next, nobiletin significantly decreased the levels of phospho-ERK2 and phospho-Akt in ERK2 or Akt siRNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. In conclusion, nobiletin attenuates HGF-induced HepG2 cells metastasis involving both ERK and PI3K/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma. <p><a href="https://greenmedinfo.com/article/nobiletin-attenuates-metastasis-both-erk-and-pi3kakt-pathways-hgf-treated-live" target="_blank">read more</a></p> https://greenmedinfo.com/article/nobiletin-attenuates-metastasis-both-erk-and-pi3kakt-pathways-hgf-treated-live#comments Cancer Metastasis Liver Cancer Nobiletin Anti-metastatic In Vitro Study Sat, 25 Jul 2020 19:49:55 +0000 greenmedinfo 224220 at https://greenmedinfo.com Resveratrol induced premature senescence and inhibited epithelial-mesenchymal transition of cancer cells via induction of tumor suppressor Rad9. https://greenmedinfo.com/article/resveratrol-induced-premature-senescence-and-inhibited-epithelial-mesenchymal- PMID:  PLoS One. 2019 ;14(7):e0219317. Epub 2019 Jul 16. PMID: 31310624 Abstract Title:  Resveratrol induced premature senescence and inhibited epithelial-mesenchymal transition of cancer cells via induction of tumor suppressor Rad9. Abstract:  Resveratrol (RSV) has been reported to influence many biological processes, including the stimulation of cellular senescence and inhibition of epithelial-mesenchymal transition (EMT). In this research, we explored the mechanisms of RSV on EMT and cellular senescence through the expression of a DNA damage response (DDR) protein, Rad9, in breast and lung cancer cell lines. Upon treating breast and lung cancer cell lines with RSV at the concentrations of 10-50μM, Rad9 expression was increased at both transcriptional and translational levels. The results indicated that RSV-induced Rad9 expression, mediated by DNA damage and ROS, can significantly suppress proliferation by activating cellular senescence, and diminishing the expression of EMT markers withconcomitant downregulation of Slug in breast and lung cancer cell lines. By using a siRNA approach, RSV was shown to mediate cellular senescence and EMT through a Rad9-dependent mechanism. The treatment with RSV can inhibit the proliferation, EMT, and increase cellular senescence of breast and lungcancer cell lines by activating Rad9. Our results suggest that the breast and lung tumor suppressive activities of RSV are, at least in part, mediated by the upregulation of Rad9. <p><a href="https://greenmedinfo.com/article/resveratrol-induced-premature-senescence-and-inhibited-epithelial-mesenchymal-" target="_blank">read more</a></p> https://greenmedinfo.com/article/resveratrol-induced-premature-senescence-and-inhibited-epithelial-mesenchymal-#comments Breast Cancer Cancer Metastasis Lung Cancer Resveratrol Antiproliferative Enzyme Inhibitors Tumor Suppressor Protein p53 Upregulation In Vitro Study Mon, 20 Jul 2020 17:54:54 +0000 greenmedinfo 223899 at https://greenmedinfo.com "Anti-metastasis effect of thymoquinone on human pancreatic cancer" https://greenmedinfo.com/article/anti-metastasis-effect-thymoquinone-human-pancreatic-cancer PMID:  Yao Xue Xue Bao. 2011 Aug ;46(8):910-4. PMID: 22007514 Abstract Title:  [Anti-metastasis effect of thymoquinone on human pancreatic cancer]. Abstract:  Recent studies reported that thymoquinone (TQ), a component derived from the medicinal spice Nigella sativa (also called black cumin), exhibited inhibitory effects on cell proliferation of many cancer cell lines. This study was performed to investigate the anti-metastatic effect of thymoquinone on the pancreatic cancer in vitro and in vivo. The results showed that thymoquinone suppressed the migration and invasion of Panc-1 cells in a does-dependent manner. To investigate the possible mechanisms involved in these events, Western blotting analysis was performed, and found that thymoquinone significantly down-regulates NF-kappaB and MMP-9 in Panc-1 cells. In addition, metastatic model simulating human pancreatic cancer was established by orthotropic implantation of histologically intact pancreatic tumor tissue into the pancreatic wall of nude mice. And administration of thymoquinone significantly reduced tumor metastasis compared to untreated control. Furthermore, the expression of NF-kappaB and MMP-9 in tumor tissues was also suppressed after treatment with thymoquinone. Taken together, the results indicate that thymoquinone exerts anti-metastatic activity on pancreatic cancer both in vitro and in vivo, which may be related to down-regulation of NF-kappaB and its regulated molecules such as MMP-9 protein. Consequently, these results provide important insights into thymoquinone as an antimetastatic agent for the treatment of human pancreatic cancer. https://greenmedinfo.com/article/anti-metastasis-effect-thymoquinone-human-pancreatic-cancer#comments Cancer Metastasis Pancreatic Cancer: Metastatic Thymoquinone Anti-metastatic Animal Study Wed, 19 Dec 2012 19:51:04 +0000 greenmedinfo 87224 at https://greenmedinfo.com "Antineoplaston AS2-1 showed an antimetastatic effect against post-operative lung metastases from colon cancer through G1 cell arrest and the subsequent induction of apoptosis." https://greenmedinfo.com/article/antineoplaston-as2-1-showed-antimetastatic-effect-against-post-operative-lung- PMID:  Oncol Rep. 2005 Mar ;13(3):389-95. PMID: 15706406 Abstract Title:  Effects of antineoplaston AS2-1 against post-operative lung metastasis in orthotopically implanted colon cancer in nude rat. Abstract:  We have investigated the efficacy and mechanisms of antineoplaston AS2-1 against post-operative lung metastasis following removal of implanted human colon cancer in nude rat. The influence of AS2-1 on in vitro KM12SM human colon carcinoma cell activities (growth, cell cycle, and apoptosis) was evaluated. AS2-1 was administered perorally after removal of the implanted KM12SM cecal cancer in nude rat. AS2-1 inhibited KM12SM cell proliferation through G1 cell arrest and, at a higher concentration, induction of apoptosis. AS2-1 showed significant reduction in lung metastasis at 5 weeks after cecal removal. The survival rate in the AS2-1 group was significantly higher than that in the control. TUNEL staining on the lung metastatic tumors revealed that the apoptosis index (AI) in the AS2-1 group was significantly higher. Antineoplaston AS2-1 showed an antimetastatic effect against post-operative lung metastases from colon cancer through G1 cell arrest and the subsequent induction of apoptosis. https://greenmedinfo.com/article/antineoplaston-as2-1-showed-antimetastatic-effect-against-post-operative-lung-#comments Antineoplaston AS2-1 (4:1 mixture of phenylacetic acid and phenylacetylglutamine) Cancer Metastasis Colon Cancer Lung Cancer: Metastatic Post-Operative Lung Metastasis of Colon Cancer Anti-metastatic Apoptotic Cell cycle arrest Animal Study Sun, 22 Apr 2012 01:52:01 +0000 greenmedinfo 74602 at https://greenmedinfo.com "Aqueous extract of Tribulus terrestris Linn induces cell growth arrest and apoptosis by down-regulating NF-κB signaling in liver cancer cells." https://greenmedinfo.com/article/aqueous-extract-tribulus-terrestris-linn-induces-cell-growth-arrest-and-apopto PMID:  J Ethnopharmacol. 2011 Jun 14 ;136(1):197-203. Epub 2011 Apr 28. PMID: 21549825 Abstract Title:  Aqueous extract of Tribulus terrestris Linn induces cell growth arrest and apoptosis by down-regulating NF-κB signaling in liver cancer cells. Abstract:  ETHNOPHARMACOLOGICAL RELEVANCE: A medicinal herb Tribulus terrestris Linn has been used to treat various diseases including hepatocellular carcinoma. The aim of the present study was to investigate the anticancer activity of Tribulus terrestris Linn (TT) in liver cancer cells.MATERIALS AND METHODS: The antitumor activity of aqueous TT extract was analyzed by testing the cytotoxicity and the effect on clonogenecity in HepG2 cells. Apoptosis and cell cycle arrest induced by TT were dissected by flow cytometry and its inhibitory effect on NF-κB activity was determined by analyzing the expression levels of NF-κB/IκB subunit proteins. The suppression of NF-κB-regulated gene expression by TT was assessed by RT-PCR.RESULTS: TT extract repressed clonogenecity and proliferation, induced apoptosis, and enhanced accumulation in the G0/G1 phase of liver cancer cells. It also turned out that TT extract inhibited NF-κB-dependent reporter gene expression and NF-κB subunit p50 expression, while it enhanced the cellular level of IκBα by inhibiting the phosphorylation and degradation of IκBα. In addition, IKK activity was inhibited in a dose-dependent manner. Furthermore, TT extract suppressed the transcription of genes associated with cell cycle regulation, anti-apoptosis, and invasion.CONCLUSION: These data showed that TT extract blocks proliferation and induces apoptosis in human liver cancer cells through the inhibition of NF-κB signaling. Aqueous TT extract can be used as an anticancer drug for hepatocellular carcinoma patients. https://greenmedinfo.com/article/aqueous-extract-tribulus-terrestris-linn-induces-cell-growth-arrest-and-apopto#comments Cancer Metastasis Liver Cancer Tribulus Antiproliferative Apoptotic Cell cycle arrest NF-kappaB Inhibitor Phytotherapy Plant Extracts In Vitro Study Wed, 19 Dec 2012 21:24:22 +0000 greenmedinfo 87281 at https://greenmedinfo.com "Baicalein inhibits the migration and invasive properties of human hepatoma cells." https://greenmedinfo.com/article/baicalein-inhibits-migration-and-invasive-properties-human-hepatoma-cells PMID:  Toxicol Appl Pharmacol. 2011 Sep 15 ;255(3):316-26. Epub 2011 Jul 23. PMID: 21803068 Abstract Title:  Baicalein inhibits the migration and invasive properties of human hepatoma cells. Abstract:  Flavonoids have been demonstrated to exert health benefits in humans. We investigated whether the flavonoid baicalein would inhibit the adhesion, migration, invasion, and growth of human hepatoma cell lines, and we also investigated its mechanism of action. The separate effects of baicalein and baicalin on the viability of HA22T/VGH and SK-Hep1 cells were investigated for 24h. To evaluate their invasive properties, cells were incubated on matrigel-coated transwell membranes in the presence or absence of baicalein. We examined the effect of baicalein on the adhesion of cells, on the activation of matrix metalloproteinases (MMPs), protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK), and on tumor growth in vivo. We observed that baicalein suppresses hepatoma cell growth by 55%, baicalein-treated cells showed lower levels of migration than untreated cells, and cell invasion was significantly reduced to 28%. Incubation of hepatoma cells with baicalein also significantly inhibited cell adhesion to matrigel, collagen I, and gelatin-coated substrate. Baicalein also decreased the gelatinolytic activities of the matrix metalloproteinases MMP-2, MMP-9, and uPA, decreased p50 and p65 nuclear translocation, and decreased phosphorylated I-kappa-B (IKB)-β. In addition, baicalein reduced the phosphorylation levels of PKCα and p38 proteins, which regulate invasion in poorly differentiated hepatoma cells. Finally, when SK-Hep1 cells were grown as xenografts in nude mice, intraperitoneal (i.p.) injection of baicalein induced a significant dose-dependent decrease in tumor growth. These results demonstrate the anticancer properties of baicalein, which include the inhibition of adhesion, invasion, migration, and proliferation of human hepatoma cells in vivo. https://greenmedinfo.com/article/baicalein-inhibits-migration-and-invasive-properties-human-hepatoma-cells#comments Baicalein Cancer Metastasis Hepatoma Liver Cancer Anti-metastatic Antiproliferative In Vitro Study Sat, 31 Dec 2011 14:48:44 +0000 greenmedinfo 70426 at https://greenmedinfo.com "Bisphosphonate stimulation of osteoblasts and osteoblastic metastasis as a mechanism of hypocalcaemia." https://greenmedinfo.com/article/bisphosphonate-stimulation-osteoblasts-and-osteoblastic-metastasis-mechanism-h PMID:  Med Hypotheses. 2011 Dec 27. Epub 2011 Dec 27. PMID: 22206806 Abstract Title:  Bisphosphonate stimulation of osteoblasts and osteoblastic metastasis as a mechanism of hypocalcaemia. Abstract:  Bisphosphonates are used in the oncological setting to treat and prevent skeletal-related events and preserve bone mineral density. Bisphosphonates also possess a hypocalcaemic effect. When undesired, hypocalcaemia can result in increased morbidity and complications. The currently understood mechanism of bisphosphonate-induced hypocalcaemia is by osteoclast inhibition. The effect of bisphosphonates on osteoblasts is less well understood. Laboratory studies demonstrate that bisphosphonates increase osteoblast and osteoblastic metastases maturation, activity and bone mineralization. We hypothesize that where large populations of osteoblasts exist increased mineralization may result in hypocalcaemia. Consequently patients with bone-metastatic prostate cancer may be more susceptible to symptomatic hypocalcaemia following bisphosphonate therapy. We are currently designing a study to investigate our hypothesis and to identify the risk factors of hypocalcaemia. https://greenmedinfo.com/article/bisphosphonate-stimulation-osteoblasts-and-osteoblastic-metastasis-mechanism-h#comments Cancer Metastasis Prostate Cancer Prostate Cancer: Bone Metastatic Bisphosphonates Commentary Sun, 08 Jan 2012 20:19:37 +0000 greenmedinfo 70652 at https://greenmedinfo.com "Breast-cancer stem cells-beyond semantics." https://greenmedinfo.com/article/breast-cancer-stem-cells-beyond-semantics PMID:  Lancet Oncol. 2012 Jan ;13(1):e43-8. PMID: 22225725 Abstract Title:  Breast-cancer stem cells-beyond semantics. Abstract:  Intratumoral heterogeneity in breast cancer is well documented. Although the mechanisms leading to this heterogeneity are not understood, a subpopulation of cancer cells, cancer stem cells (CSCs), that have some phenotypic similarities with adult tissue stem cells, has been suggested to contribute to tumour heterogeneity. It has been postulated that these CSCs are dormant, and by virtue of their low proliferative activity and ability to exclude intracellular toxins, are resistant to chemotherapy and radiation therapy. These cells were initially isolated based on the presence of markers such as CD44, CD24, and ALDH1, with further characterisation using mammosphere assay and transplantation into immunodeficient mice. The CSC hypothesis raises several theoretical and practical questions. Does cancer arise in normal mammary stem cells or do some malignant cells acquire a CSC phenotype through clonal evolution? Are CSCs in different molecular (intrinsic) subtypes of breast cancer similar, or do they have distinct properties based on the subtype? Does the CSC phenotype reflect plasticity or the dynamic nature of a few cancer cells? How do these cells acquire invasive behaviour, as they go through epithelial-to-mesenchymal transition and then revert to epithelial phenotype at sites of metastasis in response to tumour microenvironmental and metastasis site-specific cues? It is increasingly recognised that the methods and assays used for identifying CSCs have substantial limitations; does this negate the entire concept? In this Personal View, we argue that the CSC phenotype represents an aggressive clone that survives in an adverse environment through constant evolution and integration of various hallmarks of cancer. This evolution could involve acquiring mutations that permit asymmetric and symmetric division, converting the host immune attack to its own advantage, and plasticity to adapt to sites of metastasis through reversible change in adhesion molecules. We also argue that the cell-type origin of cancer could affect the rate at which CSCs develop in a tumour, with an eventual effect on disease outcome. https://greenmedinfo.com/article/breast-cancer-stem-cells-beyond-semantics#comments Breast Cancer Breast Cancer Stem Cells Cancer Metastasis Cancer Stem Cells Review Tue, 17 Jul 2012 16:37:00 +0000 greenmedinfo 78630 at https://greenmedinfo.com "Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2." https://greenmedinfo.com/article/curcumin-inhibits-prostate-cancer-metastasis-vivo-targeting-inflammatory-cytok PMID:  Carcinogenesis. 2012 Dec ;33(12):2507-19. Epub 2012 Oct 5. PMID: 23042094 Abstract Title:  Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2. Abstract:  In America and Western Europe, prostate cancer is the second leading cause of death in men. Emerging evidence suggests that chronic inflammation is a major risk factor for the development and metastatic progression of prostate cancer. We previously reported that the chemopreventive polyphenol curcumin inhibits the expression of the proinflammatory cytokines CXCL1 and -2 leading to diminished formation of breast cancer metastases. In this study, we analyze the effects of curcumin on prostate carcinoma growth, apoptosis and metastasis. We show that curcumin inhibits translocation of NFκB to the nucleus through the inhibition of the IκB-kinase (IKKβ, leading to stabilization of the inhibitor of NFκB, IκBα, in PC-3 prostate carcinoma cells. Inhibition of NFκB activity reduces expression of CXCL1 and -2 and abolishes the autocrine/paracrine loop that links the two chemokinesto NFκB. The combination of curcumin with the synthetic IKKβ inhibitor, SC-541, shows no additive or synergistic effects indicating that the two compounds share the target. Treatment of the cells with curcumin and siRNA-based knockdown of CXCL1 and -2 induce apoptosis, inhibit proliferation and downregulate several important metastasis-promoting factors like COX2, SPARC and EFEMP. In an orthotopic mouse model of hematogenous metastasis, treatment with curcumin inhibits statistically significantly formation of lung metastases. In conclusion, chronic inflammation can induce a metastasis pronephenotype in prostate cancer cells by maintaining a positive proinflammatory and prometastatic feedback loop between NFκB and CXCL1/-2. Curcumin disrupts this feedback loop by the inhibition of NFκB signaling leading to reduced metastasis formation in vivo. https://greenmedinfo.com/article/curcumin-inhibits-prostate-cancer-metastasis-vivo-targeting-inflammatory-cytok#comments Cancer Metastasis Curcumin Prostate Cancer Prostate Cancer: Metastatic Anti-metastatic Antineoplastic Agents Apoptotic NF-kappaB Inhibitor In Vitro Study Tue, 12 Mar 2013 16:55:29 +0000 greenmedinfo 93076 at https://greenmedinfo.com "HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion." https://greenmedinfo.com/article/her2-regulates-mammary-stemprogenitor-cell-population-driving-tumorigenesis-an PMID:  Oncogene. 2008 Oct 16 ;27(47):6120-30. Epub 2008 Jun 30. PMID: 18591932 Abstract Title:  HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Abstract:  The cancer stem cell hypothesis proposes that cancers arise in stem/progenitor cells through disregulation of self-renewal pathways generating tumors, which are driven by a component of &#039;tumor-initiating cells&#039; retaining stem cell properties. The HER2 gene is amplified in 20-30% of human breast cancers and has been implicated in mammary tumorigenesis as well as in mediating aggressive tumor growth and metastasis. We demonstrate that HER2 overexpression drives mammary carcinogenesis, tumor growth and invasion through its effects on normal and malignant mammary stem cells. HER2 overexpression in normal mammary epithelial cells (NMEC) increases the proportion of stem/progenitor cells as demonstrated by in vitro mammosphere assays and the expression of stem cell marker aldehyde dehydrogenase (ALDH) as well as by generation of hyperplastic lesions in humanized fat pads of NOD (nucleotide-binding oligomerization domain)/SCID (severe combined immunodeficient) mice. Overexpression of HER2 in a series of breast carcinoma cell lines increases the ALDH-expressing &#039;cancer stem cell&#039; population which displays increased expression of stem cell regulatory genes, increased invasion in vitro and increased tumorigenesis in NOD/SCID mice. The effects of HER2 overexpression on breast cancer stem cells are blocked by trastuzumab in sensitive, but not resistant, cell lines, an effect mediated by the PI3-kinase/Akt pathway. These studies provide support for the cancer stem cell hypothesis by suggesting that the effects of HER2 amplification on carcinogenesis, tumorigenesis and invasion may be due to its effects on normal and malignant mammary stem/progenitor cells. Furthermore, the clinical efficacy of trastuzumab may relate to its ability to target the cancer stem cell population in HER2-amplified tumors. https://greenmedinfo.com/article/her2-regulates-mammary-stemprogenitor-cell-population-driving-tumorigenesis-an#comments Breast Cancer Cancer Metastasis Cancer Stem Cells Antiproliferative Cancer Stem Cells HER-2 Oncoprotein Review Fri, 27 Apr 2012 20:14:35 +0000 greenmedinfo 74987 at https://greenmedinfo.com "Inhibition of breast cancer cell invasion by melatonin is mediated through regulation of the p38 mitogen-activated protein kinase signaling pathway." https://greenmedinfo.com/article/inhibition-breast-cancer-cell-invasion-melatonin-mediated-through-regulation-p PMID:  Breast Cancer Res. 2010 ;12(6):R107. Epub 2010 Dec 17. PMID: 21167057 Abstract Title:  Inhibition of breast cancer cell invasion by melatonin is mediated through regulation of the p38 mitogen-activated protein kinase signaling pathway. Abstract:  INTRODUCTION: The pineal gland hormone, melatonin, has been shown by numerous studies to inhibit the proliferation of estrogen receptorα (ERα)-positive breast cancer cell lines. Here, we investigated the role of melatonin in the regulation of breast cancer cell invasion. METHODS: Three invasive MCF-7 breast cancer cell clones - MCF-7/6, MCF-7/Her2.1, and MCF-7/CXCR4 cells - were employed in these studies. All three cell lines exhibited elevated phosphorylation of the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) as determined by Western blot analysis. The effect of melatonin on the invasive potential of these human breast cancer cells was examined by matrigel invasion chamber assays. The expression and proteinase activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blot analysis and gelatin zymography, respectively. RESULTS: Melatonin (10-9 M) significantly suppressed the invasive potential of MCF-7/6 and MCF-7/Her2.1 cells as measured by matrigel invasion chamber assays, and significantly repressed the proteinase activity of MMP-2 and MMP-9. In MCF-7/CXCR4 cells, melatonin significantly inhibited stromal-derived factor-1 (SDF-1/CXCL12) induced cell invasion and activity of MMP-9. Elevated expression of the MT1 melatonin receptor further enhanced, while luzindole, an MT1/MT2 antagonist, abrogated melatonin&#039;s anti-invasive effect, suggesting that melatonin&#039;s effect on invasion is mediated, principally, through the MT1 receptor. Furthermore, melatonin repressed the phosphorylation of p38 MAPK in MCF-7/Her2.1 cells and blocked stromal-derived factor-1 (SDF-1) induced p38 phosphorylation in MCF-7/CXCR4 cells. SB230580, a p38 inhibitor, was able to mimic, while transfection of the cells with a constitutively-active MKK6b construct blocked melatonin&#039;s effect on cell invasion, suggesting that the anti-invasive action of melatonin is mediated through the p38 pathway. CONCLUSIONS: Melatonin exerts an inhibitory effect on breast cancer cell invasion through down-regulation of the p38 pathway, and inhibition of MMP-2 and MMP-9 expression and activity. https://greenmedinfo.com/article/inhibition-breast-cancer-cell-invasion-melatonin-mediated-through-regulation-p#comments Breast Cancer Cancer Metastasis Melatonin P38 Mitogen-Activated Protein Kinase Modulator In Vitro Study Tue, 05 Mar 2013 18:28:54 +0000 greenmedinfo 92693 at https://greenmedinfo.com "Resveratrol inhibits tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells." https://greenmedinfo.com/article/resveratrol-inhibits-tumor-necrosis-factor-alpha-mediated-matrix-metalloprotei PMID:  Biomed Pharmacother. 2008 Jul-Aug;62(6):366-72. Epub 2007 Oct 22. PMID: 17988825 Abstract Title:  Resveratrol inhibits tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells. Abstract:  Resveratrol is an active polyphenol found in red wine that has anti-cancer effects, but the molecular mechanisms of resveratrol on tumor invasion inhibition have not been well documented. The aim of this study was to elucidate the effects of resveratrol on invasion ability of human hepatocellular carcinoma cells and TNF-alpha-mediated MMP-9 expression. The expression activity of MMP-9 was measured by zymography, RT-PCR and western blot analysis. The expression of NF-kappa B was measured by EMSA and western blot analysis. TNF-alpha induced the MMP-9 expression in HepG2 cells. Resveratrol significantly inhibited TNF-alpha-mediated MMP-9 expression in HepG2 cells. NF-kappa B inhibitor induced a marked reduction in MMP-9 expression, and it suggested that NF-kappa B could play an important role in TNF-alpha-mediated MMP-9 expression. Furthermore, resveratrol significantly suppressed TNF-alpha-mediated NF-kappa B expression and invasion of HepG2 cells. Our results showed that resveratrol inhibited TNF-alpha-mediated MMP-9 expression and invasion of human hepatocellular carcinoma cells. The inhibitory effects are partly associated with the downregulation of the NF-kappa B signaling pathway. https://greenmedinfo.com/article/resveratrol-inhibits-tumor-necrosis-factor-alpha-mediated-matrix-metalloprotei#comments Cancer Metastasis Liver Cancer Resveratrol Stilbenes Matrix metalloproteinase-9 (MMP-9) inhibitor NF-kappaB Inhibitor Tumor Necrosis Factor (TNF) Alpha Inhibitor In Vitro Study Sat, 31 Dec 2011 22:44:05 +0000 greenmedinfo 70481 at https://greenmedinfo.com 2-Hydroxychalcone and xanthohumol inhibit invasion of triple negative breast cancer cells. https://greenmedinfo.com/article/2-hydroxychalcone-and-xanthohumol-inhibit-invasion-triple-negative-breast-canc PMID:  Chem Biol Interact. 2013 May 25 ;203(3):565-72. Epub 2013 Apr 3. PMID: 23562496 Abstract Title:  2-Hydroxychalcone and xanthohumol inhibit invasion of triple negative breast cancer cells. Abstract:  Breast cancer is estimated as one of the most common causes of cancer death among women. In particular, triple negative breast cancers (TNBCs), which do not express the genes for estrogen/progesterone receptors (ER/PR) and human epidermal growth factor receptor 2 (HER2), have been associated with poor prognosis and metastasis. Chalcones, the biosynthetic precursors of flavonoids present in edible plants, exert cytotoxic and chemopreventive activities. Although mounting evidence suggests the anticancer properties of chalcones, limited information is available regarding the inhibitory effects of chalcones on the aggressiveness of breast cancer cells. The present study aimed to investigate the effects of chalcone and its derivatives on the growth and the invasiveness of TNBC cells. Here, we showed that treatment with chalcone, 2-hydroxychalcone, and xanthohumol for 24h inhibited the growth of MDA-MB-231 cells with IC50 values of 18.1, 4.6, and 6.7μM, respectively. Similarly, Chalcone, 2-hydroxychalcone, and xanthohumol also exerted cytotoxicity in another TNBC cell line, Hs578T. Neohesperidin dihydrochalcone, 4-methoxychalcone, and hesperidin methylchalcone did not show the cytotoxicity on the MDA-MB-231 cells. Xanthohumol and 2-hydroxychalcone induced apoptosis by Bcl-2 downregulation. Importantly, 2-hydroxychalcone and xanthohumol exerted more potent inhibitory effects on the proliferation, MMP-9 expression and invasive phenotype of MDA-MB-231 than chalcone. These results suggest a potential application of these chalcones as anticancer agents that can alleviate malignant progression of TNBC. <p><a href="https://greenmedinfo.com/article/2-hydroxychalcone-and-xanthohumol-inhibit-invasion-triple-negative-breast-canc" target="_blank">read more</a></p> https://greenmedinfo.com/article/2-hydroxychalcone-and-xanthohumol-inhibit-invasion-triple-negative-breast-canc#comments Breast Cancer Breast Cancer: Triple Negative Cancer Metastasis Xanthohumol Anti-metastatic Antineoplastic Agents Antiproliferative Apoptotic In Vitro Study Sun, 11 Nov 2018 02:27:23 +0000 greenmedinfo 173773 at https://greenmedinfo.com 6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion. https://greenmedinfo.com/article/6-shogaol-active-constituent-ginger-inhibits-breast-cancer-cell-invasion PMID:  Br J Pharmacol. 2010 Dec ;161(8):1763-77. PMID: 20718733 Abstract Title:  6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation. Abstract:  BACKGROUND AND PURPOSE: Shogaols are reported to possess anti-inflammatory and anticancer activities. However, the antimetastatic potential of shogaols remains unexplored. This study was performed to assess the effects of shogaols against breast cancer cell invasion and to investigate the underlying mechanisms.EXPERIMENTAL APPROACH: The anti-invasive effect of a series of shogaols was initially evaluated on MDA-MB-231 breast cancer cells using the matrigel invasion assay. The suppressive effects of 6-shogaol on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and nuclear factor-κB (NF-κB) activation were further determined.KEY RESULTS: Shogaols (6-, 8- and 10-shogaol) inhibited PMA-stimulated MDA-MB-231 cell invasion with an accompanying decrease in MMP-9 secretion. 6-Shogaol was identified to display the greatest anti-invasive effect in association with a dose-dependent reduction in MMP-9 gene activation, protein expression and secretion. The NF-κB transcriptional activity was decreased by 6-shogaol; an effect mediated by inhibition of IκB phosphorylation and degradation that subsequently led to suppression of NF-κB p65 phosphorylation and nuclear translocation. In addition, 6-shogaol was found to inhibit JNK activation with no resultingreduction in activator protein-1 transcriptional activity. By using specific inhibitors, it was demonstrated that ERK and NF-κB signalling, but not JNK and p38 signalling, were involved in PMA-stimulated MMP-9 activation.CONCLUSIONS AND IMPLICATIONS: 6-Shogaol is a potent inhibitor of MDA-MB-231 cell invasion, and the molecular mechanism involves at least in part the down-regulation of MMP-9 transcription by targeting the NF-κB activation cascade. This class of naturally occurring small molecules thus have potential for clinical use as antimetastatic treatments. https://greenmedinfo.com/article/6-shogaol-active-constituent-ginger-inhibits-breast-cancer-cell-invasion#comments 6-Shogaol Breast Cancer Breast Cancer: Metastatic Cancer Metastasis Anti-metastatic Antineoplastic Agents Matrix metalloproteinase-9 (MMP-9) inhibitor NF-kappaB Inhibitor In Vitro Study Sat, 18 Feb 2012 02:59:44 +0000 greenmedinfo 72846 at https://greenmedinfo.com A cannabinoid quinone has anti-angiogenic and anticancer activity. https://greenmedinfo.com/article/cannabinoid-quinone-has-anti-angiogenic-and-anticancer-activity PMID:  Mol Pharmacol. 2006 Jul;70(1):51-9. Epub 2006 Mar 29. PMID: 16571653 Abstract Title:  A cannabinoid quinone inhibits angiogenesis by targeting vascular endothelial cells. Abstract:  Recent findings on the inhibition of angiogenesis and vascular endothelial cell proliferation by anthracycline antibiotics, which contain a quinone moiety, make this type of compound a very promising lead in cancer research/therapy. We have reported that a new cannabinoid anticancer quinone, cannabidiol hydroxyquinone (HU-331), is highly effective against tumor xenografts in nude mice. For evaluation of the antiangiogenic action of cannabinoid quinones, collagen-embedded rat aortic ring assay was used. The ability of cannabinoids to cause endothelial cell apoptosis was assayed by TUNEL staining and flow cytometry analysis. To examine the genes and pathways targeted by HU-331 in vascular endothelial cells, human cDNA microarrays and polymerase chain reaction were used. Immunostaining with anti-CD31 of tumors grown in nude mice served to indicate inhibition of tumor angiogenesis. HU-331 was found to be strongly antiangiogenic, significantly inhibiting angiogenesis at concentrations as low as 300 nM. HU-331 inhibited angiogenesis by directly inducing apoptosis of vascular endothelial cells without changing the expression of pro- and antiangiogenic cytokines and their receptors. A significant decrease in the total area occupied by vessels in HU-331-treated tumors was also observed. These data lead us to consider HU-331 to have high potential as a new antiangiogenic and anticancer drug.   https://greenmedinfo.com/article/cannabinoid-quinone-has-anti-angiogenic-and-anticancer-activity#comments Cancer Metastasis Cancers: All Marijuana Anti-Angiogenic Anti-Tumor In Vitro Study Sat, 07 Nov 2009 16:20:16 +0000 greenmedinfo 47677 at https://greenmedinfo.com