Ursolic acid overcomes Bcl‐2‐mediated resistance to apoptosis in prostate cancer cells involving activation of JNK‐induced Bcl‐2 phosphorylation and degradation |
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Authors: | Yu‐xi Zhang Chui‐ze Kong Lin‐hui Wang Jin‐yi Li Xian‐kui Liu Bin Xu Chuan‐liang Xu Ying‐hao Sun |
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Institution: | 1. Department of Urology, The First Hospital of China Medical University, Shenyang 110001, China;2. Department of Urology, Shanghai Changhai Hospital, The Second Military Medical University, Shanghai 200433, China |
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Abstract: | Androgen‐independent prostate cancers express high levels of Bcl‐2, and this over‐expression of Bcl‐2 protects prostate cancer cells from undergoing apoptosis. Ursolic acid (UA) has demonstrated an anti‐proliferative effect in various tumor types. The aim of this study is to evaluate the difference between UA‐induced apoptosis in androgen‐dependent prostate cancer cell line LNCaP cells and androgen‐independent prostate cancer cell line LNCaP‐AI cells and to reveal the molecular mechanisms underlying the apoptosis. We found that UA treatment in vitro can effectively induce apoptosis in LNCaP and LNCaP‐AI cells. UA can overcome Bcl‐2‐mediated resistance to apoptosis in LNCaP‐AI cells. Intrinsic apoptotic pathways can be triggered by UA treatment because c‐Jun N‐terminal kinase (JNK) is activated and subsequently provokes Bcl‐2 phosphorylation and degradation, inducing activation of caspase‐9. Although further evaluation is clearly needed, the present results suggest the potential utility of UA as a novel therapeutic agent in advanced prostate cancer. J. Cell. Biochem. 109: 764–773, 2010. © 2009 Wiley‐Liss, Inc. |
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Keywords: | ursolic acid c‐Jun N‐terminal kinase apoptosis Bcl‐2 prostate carcinoma |
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