Exploring the Therapeutic Effects of Bisphenol-A on Prostate Cancer

Abstract

Prostate cancer (PCa) is the most common cancer in American men and its metastatic spread is responsible for its high mortality rates. Since PCa cells evolve against various treatment approaches, there is an urgent need for new treatment solutions. Bisphenol A (BPA) is an industrial chemical with structural similarities to androgens and estrogens and is postulated to interfere with androgen receptor (AR) and estrogen receptor function by competitive inhibition. Previous studies reported that low concentrations of BPA stimulate the proliferation of cancer cells expressing AR, whereas high concentrations of BPA unexpectedly inhibited the growth of those cells. This prompted the hypothesis that high concentrations of BPA might kill AR-positive, treatment-resistant PCa cells. In this study, the effect of high concentrations of BPA on AR-positive, Enzalutamide (a recent oral AR inhibitor)-resistant PCa cells were evaluated. At high concentrations, BPA was found to reduce cell growth by 90% and to trigger cell death. To explore the underlying molecular mechanisms, the expression and activity of AR were examined; both were decreased upon treatment of high BPA concentrations. In summary, high concentrations of BPA can inhibit cell growth and stimulate cell death of Enzalutamide-resistant PCa by targeting AR signaling. These findings may pave the road for novel approaches for treatment-resistant PCa.