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Evidence-Based Complementary and Alternative Medicine
Volume 2012, Article ID 580736, 11 pages
Research Article

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

1Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan
2Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan
3Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan
4Department of Education and Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan
5Department of Urology, Chang Bing Show Chwan Memorial Hospital, Changhua 50544, Taiwan
6Agricultural Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan
7Graduate Institute of Rehabilitation Science, China Medical University, Taichung 40402, Taiwan
8Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

Received 21 August 2012; Revised 9 November 2012; Accepted 16 November 2012

Academic Editor: Chun-Tao Che

Copyright © 2012 Mei-Chih Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.