Quercetin suppresses invasion and migration of H-Ras-transformed MCF10A human epithelial cells by inhibiting phosphatidylinositol 3-kinase

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.