Abstract
Abstract Background: Our previous results were the first to show that physiological concentrations (1 μM) of genistein, a soy component, in the presence of17β-estradiol (1 nM) inhibited the cell proliferation of MDA-MB-231 (Estrogen receptor (ER) β positive) breast cancer cells. These results are relevant in premenopausal women with breast cancer of the ERα-negative and ERβ-positive type, especially given the increasing trends of soy intake among the US population in the past decade. The aim of the present study was to identify the mechanism by which genistein plus 17β-estradiol inhibits the cell proliferation of ERα-negative and ERb-positive breast cancer cells. Our hypothesis is that the balance of signaling actions by genistein plus 17β-estradiol from different signaling pathways is likely to lead to the cell's choice to either proliferate or enter the apoptotic pathway. For this purpose, the effect of low and high concentrations of genistein (1 μM and 100 μM) in the presence or absence of 17β-estradiol (1 nM) was studied on the expression of cell signaling proteins involved in cell proliferation, survival and apoptosis (pERK1/2, pAkt, Bax and Bcl2) and correlated to cell proliferation and apoptosis in MDA-MB-231 (ERβ positive and ERα negative) breast cancer cells. Methods: Cell proliferation was determined by the MTT assay, apoptosis determined microscopically by the use of acridine orange and ethidium bromide dyes and the expression of cell signaling proteins by western blotting. Results: Our results show that 1μM genistein plus 17β-estradiol significantly increased apoptosis (p<0.05) as compared to the control (12.47% vs 5.87% respectively). Increased expression of Bax/Bcl2 (2.5 fold) along with a decreased expression of phosphorylated ERK1/2 (2 fold) was observed in cells treated with 1μM genistein plus 17β-estradiol as compared to the control cells. Phosphorylated Akt did not show any differences in the treatment condition as compared to the control. High concentrations of genistein (100 μM) in the presence or absence of 17β-estradiol also increased apoptosis; however these changes could not be correlated to the expression of Bax/Bcl2, or pERK1/2. Conclusion: In conclusion, our results show that physiological concentrations of genistein in the presence of17β-estradiol inhibit cell growth through apoptosis via increased Bax/Bcl2 and a concomitant decrease in pERK1/2 expression. Our results also suggest that different concentrations of genistein elicit cell responses through different signaling mechanisms. These results are especially relevant to the cohort of premenopausal women with breast cancer of the ERβ positive and ERα negative type. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-04-07.
Published Version
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