Protopine, a novel microtubule-stabilizing agent, causes mitotic arrest and apoptotic cell death in human hormone-refractory prostate cancer cell lines

被引:58
作者
Chen, Chun-Han [1 ]
Liao, Cho-Hwa [1 ]
Chang, Ya-Ling [1 ]
Guh, Jih-Hwa [2 ]
Pan, Shiow-Lin [3 ]
Teng, Che-Ming [1 ]
机构
[1] Natl Taiwan Univ, Coll Med, Inst Pharmacol, Taipei 10051, Taiwan
[2] Natl Taiwan Univ, Coll Med, Sch Pharm, Taipei 10051, Taiwan
[3] Natl Hlth Res Inst, Inst Biotechnol & Pharmaceut Res, Miaoli, Taiwan
关键词
Protopine; Microtubules; Mitotic arrest; Cdk1; Apoptosis; INHIBITS TUBULIN POLYMERIZATION; N-TERMINAL KINASE; PHOSPHORYLATION; DOCETAXEL; CYCLIN; MITOXANTRONE; PACLITAXEL; PATHWAYS; BCL-2; DESTABILIZATION;
D O I
10.1016/j.canlet.2011.09.042
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In this study, we investigated the anticancer effect of protopine on human hormone-refractory prostate cancer (HRPC) cells. Protopine exhibited an anti-proliferative effect by induction of tubulin polymerization and mitotic arrest, which ultimately led to apoptotic cell death. The data suggest that protopine increased the activity of cyclin-dependent kinase 1 (Cdk1)/cyclin B1 complex and that contributed to cell apoptosis by modulating mitochondria-mediated signaling pathways, such as Bcl-2 phosphorylation and Mcl-1 down-regulation. In conclusion, the data suggest that protopine is a novel microtubule stabilizer with anticancer activity in HRPC cells through apoptotic pathway by modulating Cdk1 activity and BcI-2 family of proteins. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:1 / 11
页数:11
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