Abrogation of G2/M arrest sensitizes curcumin-resistant hepatoma cells to apoptosis

FEBS Lett. 2008 Aug 6;582(18):2689-95. doi: 10.1016/j.febslet.2008.06.048. Epub 2008 Jul 9.

Abstract

In this study, we showed that curcumin treatment resulted in activation of Chk1-mediated G2 checkpoint, which was associated with the induction of G2/M arrest and the resistance of cancer cells to curcumin-induced apoptosis. Further investigation revealed that inhibition of Chk1 significantly abrogated G2/M arrest and sensitized curcumin-resistant cells to apoptosis via upregulation of Bad and in turn the loss of mitochondrial membrane potential. These results indicate that Chk1-mediated G2/M arrest may serve as a mechanism for curcumin resistance and Chk1 represents a potential target for the reversal of this resistance. Our findings should be helpful for clinical application of curcumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Checkpoint Kinase 1
  • Curcumin / pharmacology*
  • Drug Resistance, Neoplasm* / genetics
  • G2 Phase / drug effects
  • Humans
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Membrane Potential, Mitochondrial / drug effects
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Up-Regulation
  • bcl-Associated Death Protein / genetics
  • bcl-Associated Death Protein / physiology

Substances

  • Antineoplastic Agents
  • bcl-Associated Death Protein
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • Curcumin