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

Abstract

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.

• Authors: Chun-Han Chen, Cho-Hwa Liao, Ya-Ling Chang, Jih-Hwa Guh, Shiow-Lin Pan, Che-Ming Teng
• Journal: Cancer letters (Cancer Lett) Vol. 315 Issue 1 Pg. 1-11 (Feb 01 2012) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 22033245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Benzophenanthridines
• Berberine Alkaloids
• Tubulin Modulators
• protopine

Topics

• Apoptosis (drug effects)
• Benzophenanthridines (pharmacology)
• Berberine Alkaloids (pharmacology)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Humans
• Male
• Mitosis (drug effects)
• Neoplasms, Hormone-Dependent (drug therapy, metabolism, pathology)
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Signal Transduction (drug effects)
• Transfection
• Tubulin Modulators (pharmacology)