Physiological Concentrations of Genistein and 17 beta-Estradiol Inhibit MDA-MB-231 Breast Cancer Cell Growth by Increasing BAX/BCL-2 and Reducing pERK1/2

Aim: The aim of the present study was to identify the mechanism by which genistein and 17 beta-estradiol inhibit proliferation of MDA-MB-231 breast cancer cells. Materials and Methods: The expression of cell signaling proteins involved in cell apoptosis, proliferation, and survival (BCL-2 associated X protein, BAX; B-cell lymphoma 2, BCL-2; extracellular signal regulated kinase, pERK1/2; and protein kinase B, pAKT) were examined by western blotting, and tested whether these effects correlated with cell proliferation and apoptosis. Results: Compared to the control, 1 mu M genistein plus 1 nM 17 beta-estradiol significantly increased apoptosis, and the BAX/BCL-2 ratio, with a concomitant decrease in ERK1/2 phosphorylation. High concentrations of genistein (100 mu M) both in the presence and absence of 17 beta-estradiol also increased apoptosis; however, these changes were not correlated with the BAX/BCL-2 ratio or with phosphorylation of ERK1/2. Conclusion: These results suggest that different concentrations of genistein elicit cell responses through different signaling mechanisms. These results are especially relevant in premenopausal women with breast cancer who are on a soy diet.