Biochanin A Promotes Proliferation that Involves a Feedback Loop of MicroRNA-375 and Estrogen Receptor Alpha in Breast Cancer Cells

Background: Biochanin A and formononetin are O-methylated isoflavones that are isolated from the root of Astragalus membranaceus, and have antitumorigenic effects. Our previous studies found that formononetin triggered growth-inhibitory and apoptotic activities in MCF-7 breast cancer cells. We performed in vivo and in vitro studies to further investigate the potential effect of biochanin A in promoting cell proliferation in estrogen receptor (ER)-positive cells, and to elucidate underlying mechanisms. Methods: ER alpha-positive breast cancer cells (T47D, MCF-7) were treated with biochanin A. The MTT assay and flow cytometry were used to assess cell proliferation and apoptosis. mRNA levels of ER alpha, Bcl-2, and miR-375 were quantified using real-time polymerase chain reaction. Compared with the control, low biochanin A concentrations (2-6 mu M) stimulated ER alpha-positive cell proliferation (T47D, MCF-7). The more sensitive T47D cells were used to study the relevant signaling pathway. Results: After treatment with biochanin A, ER alpha, miR-375, and Bcl-2 expression was significantly upregulated. Additionally, in the in vivo studies, uterine weight in ovariectomized mice treated with biochanin A increased significantly. Conclusion: This study demonstrated that biochanin A promoted ER alpha-positive cell proliferation through miR-375 activation and this mechanism is possibly involving in a miR-375 and ER alpha feedback loop. Copyright (C) 2015 S. Karger AG, Basel