Effect of soy‐derived isoflavonoids on the induced growth of MCF‐7 cells by estrogenic environmental chemicals

Abstract

Isoflavonoids are natural plant compounds and possess antitumorigenic properties. Many environmental chemicals have been found to be estrogenic and can enhance tumor growth in estrogen receptor‐positive cells. In the present study, the effects of genistein, daidzein, biochanin A, formononetin, and equol on the proliferation of estrogen receptor‐positive MCF‐7 cells induced by synthetic chemicals 1‐(o‐chlorophenyl)‐1‐(p‐chlorophenyl)‐2,2,2‐trichloroethane (o,p'‐DDT), 4‐nonylphenol (4‐NP), and 5‐octylphenol (5‐OP) found in the environment were investigated. Genistein, biochanin A, equol, and to some extent daidzein, but not formononetin, at <10 μM can enhance the growth of MCF‐7 cells in the absence of environmental chemicals. Formononetin was toxic to MCF‐7 cells at the tested concentrations. The environmental chemicals 4‐NP, 5‐OP, and o,p'‐DDT and the natural estrogen 17β‐estradiol at 5, 5, and 10 μM and 5 nM, respectively, induced proliferation of MCF‐7 cells. In the presence of isoflavonoids (>25 μM), the environmental chemical‐induced cell proliferation was inhibited. Individually, genistein (IC50 = 25–33 μM) was the most potent inhibitor against the induced proliferation of MCF‐7 cells of the isoflavonoids needed for a 50% suppression of growth induced by 4‐NP, 5‐OP, and o,p'‐DDT. A mixture of isoflavonoids was the most potent inhibitor against the induced proliferation. Estrogen receptor‐dependent and ‐independent pathways could be involved in the inhibitory actions of isoflavonoids. Because it is impossible to have a chemical‐free environment, the in vitro data presented here are of practical importance to develop evolving dietary strategies and tactics against the adverse health effects of environmental chemicals.