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Volume 12, Issue 4 (July 2010) 12, 527–534; 10.1038/aja.2010.21
The multikinase inhibitor sorafenib induces caspase-dependent apoptosis in PC-3 prostate cancer cells
Rui Huang1,*, Xue-Qin Chen2,*, Ying Huang2, Ni Chen2 and Hao Zeng3
1 Department of Nuclear Medicine, National Key Discipline of Medical Imaging and Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
2 Laboratory of Pathology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
3 Department of Urology, West China Hospital, Sichuan University, Chengdu 610041, China
*These two authors contributed equally to this work.
Correspondence: Prof. Hao Zeng, kucaizeng@163.com
Received 25 December 2009; Revised 11 February 2010; Accepted 6 March 2010; Published online 17 May 2010.
| Abstract |
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The present study investigated the effects of the multikinase inhibitor sorafenib on androgen-independent cancer cells viability and intracellular signaling. Human androgen-independent PC-3 prostate cancer cells were treated with sorafenib. At concentration that suppresses extracellular signal-regulated kinase phosphorylation, sorafenib treatment reduced the mitochondrial transmembrane potential. Sorafenib also down-modulated the levels of myeloid cell leukemia 1, survivin and cellular inhibitor of apoptosis protein 2. Sorafenib induced caspase-3 cleavage and the mitochondrial release of cytochrome c. However, no nuclear translocation of apoptosis inducing factor was detected after treatment and the pan-caspase inhibitor Z-VAD-FMK had an obvious protective effect against the drug. In conclusion, sorafenib induces apoptosis through a caspase-dependent mechanism with down-regulated anti-apoptotic proteins in androgen-independent prostate cancer cells in vitro.
Keywords: apoptosis; PC-3 prostate cancer cells; prostate cancer; sorafenib
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