All-trans retinoic acid induces DU145 cell cycle arrest through Cdk5 activation.

BACKGROUND/AIMS All-trans retinoic acid (ATRA), the active form of vitamin A, plays an important role in the growth arrest of numerous types of cancer cells. It has been indicated that cyclin-dependent kinase 5 (Cdk5) activity can be affected by ATRA treatment. Our previous results demonstrate the involvement of Cdk5 in the fate of prostate cancer cells. The purpose of this study is to examine whether Cdk5 is involved in ATRA-induced growth arrest of the castration-resistant cancer cell line DU145 through up-regulating Cdk inhibitor protein, p27. METHODS DU145 cells were treated with ATRA, and cell proliferation, protein expression, and protein localization of Cdk5/p27 were examined. Cell proliferation and cell cycle distribution were also determined under Cdk5 inhibition induced by inhibitor or knockdown. RESULTS ATRA treatment inhibited DU145 cell proliferation and significantly increased p27 expression through Cdk5 up-regulation. Immunocytochemical data showed that a Cdk5 inhibitor reduced ATRA-triggered nuclear distribution of p27 in DU145 cells. The proliferation inhibition and G1 phase accumulation of DU145 cells were significantly increased by ATRA treatment, whereas Cdk5 inhibitor and siRNA could reverse these effects. CONCLUSIONS Our results demonstrate that ATRA induced growth inhibition in castration-resistant prostate cancer cells through activating Cdk5 and p27. We hope this finding will increase the knowledge of prostate cancer treatment and can be applied in patients' nutritional control in the future.