Ursolic acid overcomes Bcl-2-mediated resistance to apoptosis in prostate cancer cells involving activation of JNK-induced Bcl-2 phosphorylation and degradation.
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.
Zhang
Yu-xi
YX
Department of Urology, The First Hospital of China Medical University, Shenyang, China.
Kong
Chui-ze
CZ
Wang
Lin-hui
LH
Li
Jin-yi
JY
Liu
Xian-kui
XK
Xu
Bin
B
Xu
Chuan-liang
CL
Sun
Ying-hao
YH
D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects*; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D014315:Triterpenes; D000097245:Ursolic Acid
D000972:Antineoplastic Agents, Phytogenic; D053453:Caspase 9; D048031:JNK Mitogen-Activated Protein Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; D000097245:Ursolic Acid