Raddeanin A down‐regulates androgen receptor and its splice variants in prostate cancer
Abstract
Castration‐resistant progression of prostate cancer is a major cause of prostate cancer mortality, and increased expression and activity of the full‐length and the splice variants of androgen receptor (AR) have been indicated to drive castration resistance. Consequently, there is an urgent need to develop agents that can target both the full‐length and the splice variants of AR for more effective treatment of prostate cancer. In the present study, we showed that raddeanin A (RA), an oleanane‐type triterpenoid saponin, suppresses the transcriptional activities of both the full‐length and the splice variants of AR. This is attributable to their decreased expression as a result of RA induction of proteasome‐mediated degradation and inhibition of the transcription of the AR gene. We further showed the potential of using RA to enhance the growth inhibitory efficacy of docetaxel, the first‐line chemotherapy for prostate cancer. This study identifies RA as a new agent to target both the full‐length and the splice variants of AR and provides a rationale for further developing RA for prostate cancer treatment.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 23, 2019
- Source ID
- 10.1111/jcmm.14267
Entities
People
- Bryan Y. Zhang
- Cheng Hu
- Hongyan Xia
- Jing Lyu
- Lijing Zhao
- Shanshan Bai
- Xianghui Yu
- Yan Dong
- Yang Zhan
Organizations
- Congressionally Directed Medical Research Programs
- Jilin University
- National Cancer Institute
- National Natural Science Foundation of China
- The Willow School
- Tulane University of Louisiana