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

Cancer Lett. 2012 Feb 1;315(1):1-11. doi: 10.1016/j.canlet.2011.09.042. Epub 2011 Oct 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / pathology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Signal Transduction / drug effects
  • Transfection
  • Tubulin Modulators / pharmacology*

Substances

  • Benzophenanthridines
  • Berberine Alkaloids
  • Tubulin Modulators
  • protopine