Casticin inhibits AKR1C3 and enhances abiraterone efficacy in castration-resistant prostate cancer.

ABSTRACT: Castration-resistant prostate cancer (CRPC) continues to represent a critical therapeutic hurdle owing to its resistance to both androgen deprivation and next-generation antiandrogens like abiraterone (ABI). One of the key mechanisms underlying this resistance involves overexpression of aldo-keto reductase 1C3 (AKR1C3), an enzyme contributing to intratumoral androgen biosynthesis. In this study, casticin (CAS), a flavonoid derived from Vitex agnus-castus, was identified as a potent inhibitor of AKR1C3. CAS showed potent inhibitory activity in enzymatic assays (IC₅₀ = 5.99 µM), significantly suppressed AKR1C3-mediated coumberone metabolism in 22Rv1 prostate cancer cells, and showed greater cytotoxicity in AKR1C3-expressing 22Rv1 cells relative to AKR1C3-deficient LNCaP cells. CAS significan

SUBMITTER: Piska K 

PROVIDER: S-EPMC12847094 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature