Protopine, a novel microtubule-stabilizing agent, causes mitotic arrest and apoptotic cell death in human hormone-refractory prostate cancer cell lines.
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 Bcl-2 family of proteins.
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, ROC.
Chun-Han
CH
Chen
Cho-Hwa
CH
Liao
Ya-Ling
YL
Chang
Jih-Hwa
JH
Guh
Shiow-Lin
SL
Pan
Che-Ming
CM
Teng
D017209:Apoptosis / Q000187:drug effects*; D053119:Benzophenanthridines / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D008938:Mitosis / Q000187:drug effects*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D050257:Tubulin Modulators / Q000494:pharmacology*
D053119:Benzophenanthridines; D001600:Berberine Alkaloids; D050257:Tubulin Modulators; C009093:protopine