The effect of the phytoestrogens genistein, daidzein, and equol on the growth of tamoxifen-resistant T47D/PKC alpha

Soy supplements are often consumed by women for alleviating menopausal symptoms or for the perceived protective effects against breast cancer. More concerning is the concurrent consumption of soy isoflavones with tamoxifen (TAM) for prevention or treatment of breast cancer. We previously described a T47D:A18/protein kinase C (PKC)alpha TAM-resistant tumor model that exhibits autonomous growth and estradiol-induced tumor regression. We compared the estrogenicity of the isoflavones genistein, daidzein, and the daidzein metabolite equol in the parental T47D:A18 and T47D:A18/PKC alpha cell lines in vitro and in vivo. Whereas equol exerts estrogenic effects on T47D:A18 cells in vitro, none of the isoflavones stimulated T47D:A18 tumor growth. T47D:A18/PKC alpha tumor growth was partially stimulated by genistein, yet partially inhibited by daidzein. Interestingly, coadministration of TAM with either daidzein or genistein produced tumors of greater size than with TAM alone. These findings suggest that simultaneous consumption of isoflavone supplements with TAM may not be safe.