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

14 Citations (Scopus)

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 - 2012

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Tretinoin
Prostatic Neoplasms
Apoptosis
Annexin A5
Chemoprevention
G1 Phase
Caspase 3
Androgens
Therapeutics
History
Cell Proliferation
Staining and Labeling
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Retinoic acid induces apoptosis of prostate cancer DU145 cells through Cdk5 overactivation. / Chen, Mei Chih; Huang, Chih Yang; Hsu, Shih Lan; Lin, Eugene; Ku, Chien Te; Lin, Ho; Chen, Chuan Mu.

In: Evidence-based Complementary and Alternative Medicine, Vol. 2012, 580736, 2012.

Research output: Contribution to journalArticle

Chen, Mei Chih ; Huang, Chih Yang ; Hsu, Shih Lan ; Lin, Eugene ; Ku, Chien Te ; Lin, Ho ; Chen, Chuan Mu. / Retinoic acid induces apoptosis of prostate cancer DU145 cells through Cdk5 overactivation. In: Evidence-based Complementary and Alternative Medicine. 2012 ; Vol. 2012.
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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.",
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AU - Ku, Chien Te

AU - Lin, Ho

AU - Chen, Chuan Mu

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