Genistein resists castration-resistant prostate cancer by inhibiting the androgen receptor pathway

Prostate cancer is a prevalent malignancy, often diagnosed at advanced stages and associated with poor prognosis. Genistein, a soybean isoflavone, has demonstrated antitumor effects against castration-resistant prostate cancer <i>in vivo</i>. Our results indicate that genistein effectively downregulates the expression of key enzymes involved in the <i>de novo</i> synthesis pathway, namely AKR1C3, SRD5A2, CYP11A1, and 3βHSD, thus blocking androgen synthesis in CRPC cells. Additionally, genistein inhibits the activation and nuclear translocation of the AR. Collectively, these findings support the potential of genistein as a therapeutic agent for CRPC, highlighting its role in both inhibiting androgen synthesis and disrupting AR signaling.