title: Quercetin suppresses invasion and migration of H-Ras-transformed MCF10A human epithelial cells by inhibiting phosphatidylinositol 3-kinase.
abstract: Quercetin is a major flavonoid compound found in red wine at a much higher concentration than the phytoalexin resveratrol. In this study, we examined potential anti-metastatic effects and found that compared to resveratrol, quercetin more potently inhibits H-Ras-induced invasion and migration in MCF10A human epithelial cells, an effect likely mediated by the mitigation of matrix metalloproteinase (MMP)-2 activation. We then measured Akt phosphorylation to investigate whether the decreased MMP-2 activation was attributable to the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signalling. Quercetin, but not resveratrol at equivalent concentrations, suppressed the phosphorylation of Akt and was a more potent inhibitor of PI3K activity than resveratrol. An ex vivo binding assay further revealed that quercetin directly binds to PI3K. Collectively, these results suggest that PI3K is a molecular target of quercetin for the inhibition of H-Ras-induced invasion and migration of MCF10A cells.
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology, and Center for Food, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Nu Ry
authors.initials: NR
authors.lastname: Song
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Chung
authors.forename: Nam Joo
authors.initials: NJ
authors.lastname: Kang
authors.forename: Sang Gwon
authors.initials: SG
authors.lastname: Seo
authors.forename: Tae Su
authors.initials: TS
authors.lastname: Jang
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D011905:Genes, ras; D006801:Humans; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology; D014920:Wine / Q000032:analysis
chemical_list: D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016283:Proto-Oncogene Proteins p21(ras); D011794:Quercetin; D000077185:Resveratrol; D013267:Stilbenes
keywords: Cell invasion; Cell migration; MMP-2; PI3K; Quercetin