The mechanisms of apoptotic response to Resveratrol in metastatic breast cancer cells

Abstract

Resveratrol, a phytoalexin found abundantly in grapes and other grape-related products, has been shown to be antiproliferative and protective against various types of cancers, including breast cancer. However, the precise underlying mechanisms are not well understood. In this study, we show that treatment with Resveratrol inhibits cell growth of a highly invasive and metastatic breast cancer cell line MDA-MB-231 by inducing apoptosis. RSVL-induced apoptosis correlates with sustained activation of ERK1/2 and suppression of Bcl-2 expression. Inhibition of ERK1/2 activation by its specific inhibitor or small interfering RNA abrogates Resveratrol-induced apoptosis and reverses the effect of Resveratrol on Bcl-2 suppression, while overexpression of MEK1, which is direct upstream of both ERK1/2, enhances apoptosis induced by Resveratrol. The other closely related MAPK members, p38 and JNK are not involved in apoptosis induced by Resveratrol in MDA-MB-231 cells. These results suggest that activation of ERK1/2 is required for Resveratrol-induced apoptosis in MDA-MB-231 cells.