Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

Biochem Biophys Res Commun. 2012 Feb 3;418(1):98-103. doi: 10.1016/j.bbrc.2011.12.141. Epub 2012 Jan 5.


Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitotic drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimitotic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Colchicine / pharmacology
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • DNA Damage
  • Docetaxel
  • Drug Resistance, Neoplasm / drug effects*
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Paclitaxel / pharmacology
  • Pyrans / pharmacology*
  • Taxoids / pharmacology
  • Vinblastine / pharmacology


  • Antimitotic Agents
  • Cyclin-Dependent Kinase Inhibitor p21
  • Pyrans
  • Taxoids
  • Cyclin D1
  • Docetaxel
  • Vinblastine
  • salinomycin
  • Paclitaxel
  • Colchicine