Retinoic Acid Induces Apoptosis of Prostate Cancer DU145 Cells through Cdk5 Overactivation

• Published in: Evidence-based complementary and alternative medicine Vol. 2012; no. 2012; pp. 1 - 11
• Main Authors: Chen, Chuan-Mu, Ku, Chien-Te, Lin, Eugene, Hsu, Shih-Lan, Huang, Chih-Yang, Chen, Mei-Chih, Lin, Ho
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2012; Hindawi Limited
• Subjects: Acids; Activation; Androgens; Annexin V; Apoptosis; Biotechnology; Calpain; Cancer therapies; Caspase; Caspase-3; Cell cycle; Cell growth; Cell proliferation; Chemotherapy; Cleavage; Cyclin-dependent kinase 5; Endocrinology; G1 phase; Kinases; Medical research; Molecular chains; Molecular modelling; Prostate; Prostate cancer; Retinoic acid; United States > US
• ISSN: 1741-427X; 1741-4288
• DOI: 10.1155/2012/580736

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.