Retinoic acid induces apoptosis of prostate cancer DU145 cells through Cdk5 overactivation

Mei Chih Chen, Chih Yang Huang, Shih Lan Hsu, Eugene Lin, Chien Te Ku, Ho Lin, Chuan Mu Chen

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number580736
JournalEvidence-based Complementary and Alternative Medicine
Volume2012
DOIs
StatePublished - Dec 1 2012

ASJC Scopus subject areas

  • Complementary and alternative medicine

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