Retinoic acid (RA) has been believed to be an anticancer drug for a long history.
However, the molecular mechanisms of RA actions on cancer cells remain diverse. In this study, the dose-dependent inhibition of RA on DU145 cell proliferation was identified. Interestingly, RA treatment triggered p35 cleavage (p25 formation) and Cdk5 overactivation, and all could be blocked by Calpain inhibitor, Calpeptin (CP). Subsequently, RA-triggered DU145 apoptosis detected by sub-G1 phase accumulation and Annexin V staining could also be blocked by CP treatment. Furthermore, RA-triggered caspase 3 activation and following Cdk5 over-activation were destroyed by treatments of both CP and Cdk5 knockdown. In conclusion, we report a new mechanism in which RA could cause apoptosis of androgen-independent prostate cancer cells through p35 cleavage and Cdk5 over-activation. This finding may contribute to constructing a clearer image of RA function and bring RA as a valuable chemoprevention agent for prostate cancer patients.
Written by:
Chen MC, Huang CY, Hsu SL, Lin E, Ku CT, Lin H, Chen CM. Are you the author?
Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan.
Reference: Evid Based Complement Alternat Med. 2012;2012:580736
doi: 10.1155/2012/580736
PubMed Abstract
PMID: 23304206
