Androgen receptor splice variant-7 (AR-V7), an androgen-insensitive transcription factor, plays an essential role in the development of castration-resistant prostate cancer (CRPC). Enzalutamide and abiraterone can not efficiently inhibit CRPC with AR-V7 expression. Caffeic acid phenethyl ester (CAPE) is a bioactive component extracted from honeybee hive propolis. We previously reported that CAPE treatment suppresses cell proliferation and tumor metastasis of prostate cancer cells. We thus examined if CAPE treatment can reduce expression of AR-V7. AR-V7 variant is highly expressed in 22RV1 cell line. We observed that CAPE treatment suppressed both mRNA and protein expression of AR-V7 as well as its downstream ubiquitin-conjugating enzyme 2C (UBE2C) in 22RV1 cell line. Protein stability of AR-V7 is affected by the phosphorylation of Serine 81 on AR, which is regulated by CDK1. Our data showed that CAPE reduced protein expression of CDK1 and accelerated degradation of AR-V7. In xenograft model, we observed CAPE treatment repressed tumor growth and angiogenesis of 22RV1 as well as suppressed expression of AR-V7. Our data suggested that CAPE might be a potential therapy for CRPC.
