Androgen Receptor Mutations and Estrogen Receptor-β Modulate Genistein Effects on Prostate Cancer Cells

TL;DRAbstract

Genistein is the most abundant and potent isoflavone in soy and it has an estradiol-like structure. Results from previous studies examining genistein effects on androgen receptor (AR) expression and prostate cancer (PCa) cell proliferation have been contradictory. In this study, we demonstrated that these mixed results can be attributed to the use of LNCaP cells that has a promiscuous AR attributed to the presence of the T877A mutation, without comparison to cells with wild-type AR (WT-AR). We demonstrated using in silico modeling that genistein is able to bind with higher affinity to the promiscuously mutant AR than to the WT-AR. Our in vitro studies showed that low, physiological concentrations of genistein inhibited cell proliferation and AR expression and activity in presence of WT-AR. However, in the presence of mutant type of AR (MT-AR), corresponding doses induced stimulatory effects on AR expression and cell proliferation. We also demonstrated that the effects of physiological

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