Green tea (−)-epigallocatechin-3-gallate down-regulates VASP expression and inhibits breast cancer cell migration and invasion by attenuating Rac1 activity

Abstract

(−)-Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound from green tea that has been shown to have anti-tumor activities such as inhibiting adhesion, migration, and proliferation of tumor cells. However, the delicate mechanisms and signaling pathways underlying the potential anticancer effects of EGCG in breast cancer cells remain unclear. The goal of this study was to examine the effects of EGCG on the migration and invasion of MCF-7 cells and to identify the signaling pathway(s) underlying the cellular response to EGCG exposure. In a concentration-dependent manner, EGCG decreased the migratory and invasive potential of MCF-7 cells with a concomitant down-regulation of vasodilator-stimulated phosphoprotein (VASP) expression and Rac1 activity. Using specific siRNAs to block the expression of VASP and Rac1 in MCF-7 cells that were previously treated with epidermal growth factor (EGF), we demonstrated that the regulation of cell migration and invasion was associated with Rac1 activity and VASP expression. In addition, siRNA mediated knock-down of Rac1 decreased the amount of VASP expression at the mRNA level while VASP specific siRNA revealed no effect on the expression of Rac1 in MCF-7 cells. These findings suggest that the inhibitory effect of EGCG on MCF-7 cell migration and invasion may be produced by a down regulation of VASP expression via the Rac1 pathway.