Curcumin sensitizes lung cancer cells to cisplatin-induced apoptosis through superoxide anion-mediated Bcl-2 degradation

Cancer Invest. 2009 Jul;27(6):624-35. doi: 10.1080/07357900802653472.

Abstract

The purpose of this study was to investigate the sensitizing effect of curcumin on cisplatin-induced apoptosis in non-small cell lung cancer (NSCLC) H460 cells. Curcumin was shown to induce superoxide anion generation, down-regulate anti-apoptotic Bcl-2 protein, and subsequently sensitize cells to cisplatin-induced apoptosis. Co-treatment of the cells with curcumin and cisplatin resulted in increased apoptosis and reversal of Bcl-2-mediated cisplatin resistance. The mechanism by which curcumin down-regulates Bcl-2 and sensitizes cells to cisplatin-induced apoptosis involves proteasomal degradation of Bcl-2. These findings indicate a novel pathway for curcumin regulation of Bcl-2, which could benefit the development of a cisplatin sensitizing agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Curcumin / pharmacology
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Drug Resistance, Neoplasm
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Processing, Post-Translational / drug effects*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Superoxides / metabolism*
  • Time Factors
  • Transfection

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Superoxides
  • Proteasome Endopeptidase Complex
  • Curcumin
  • Cisplatin