Effects of the dietary phytoestrogen biochanin A on cell growth in the mammary carcinoma cell line MCF-7

Studies of the dietary phytoestrogen biochanin A an cell proliferation of t he cultured estrogen responsive cells human breast carcinoma MCF-7 showed t hat biochanin A exhibits biphasic regulation on MCF-7 cells. At concentrati ons of less than 10 mu g/mL, cells respond to biochanin A by increasing cel l growth and de novo DNA synthesis. The addition of biochanin A at concentr ations of greater than 30 mu g/mL. significantly inhibited cell growth and DNA synthesis in a dose-dependent fashion, resulting in an IC50 value of 40 mu g/mL. The reversibility of these inhibitory effects by biochanin A appe ars also to be concentration dependent. Cells previously treated with high concentrations (>60 mu g/mL) of biochanin A did not regain normal growth af ter treatment ceased. Biochanin A was cytostatic at low concentrations (<40 mu g/mL) and cytotoxic at higher concentrations. Upon exposure to 100 mu g /mL of biochanin A, cell morphology was severely altered, cell volume decre ased, and condensation of cell components was clearly noticeable. In additi on, biochanin A damaged cell membranes by increasing membrane permeability. These results suggest possible molecular and cellular mechanisms of the ac tion of dietary phytoestrogens on estrogen target cells. (J. Nutr. Biochem. 10:510-517, 1999) (C) Elsevier Science Inc. 1999. All rights reserved.