Icaritin inhibits castration-resistant prostate cancer via RhoB-mediated Akt signaling.

Current therapeutic regimens for castration-resistant prostate cancer (CRPC) are plagued by multiple limitations. RhoB has emerged as a promising molecular target for prostate cancer (PCa) therapy. Icaritin, a bioactive prenylated flavonoid isolated from Epimedii Folium, exhibits potent antitumor and osteogenic properties. However, the anti-CRPC efficacy of icaritin and its underlying molecular mechanisms remain incompletely elucidated. Herein, we evaluated the anti-CRPC potential of icaritin and investigated the involvement of RhoB signaling. Results demonstrated that icaritin significantly suppressed the viability, proliferation, and clonogenic capacity of CRPC cells. Furthermore, in an RM-1 xenograft model, icaritin inhibited tumor growth and reduced serum levels of prostate-specific antigen (PSA) and testosterone. Integrated RNA-seq analysis and The Cancer Genome Atlas-Prostate Adenocarcinoma (TCGA-PRAD) dataset identified RhoB as a candidate therapeutic target in CRPC. Subsequent mechanistic investigations revealed that icaritin inhibits CRPC progression by modulating RhoB-mediated Akt signaling. Collectively, these findings indicate that the anti-CRPC activity of icaritin is at least partially mediated through the RhoB/Akt signaling, providing a pharmacological basis for the further development of icaritin as a potential therapeutic agent against CRPC.