Inhibitory effect of curcumin on oral carcinoma CAL-27 cells via suppression of Notch-1 and NF-κB signaling pathways

J Cell Biochem. 2011 Apr;112(4):1055-65. doi: 10.1002/jcb.23019.

Abstract

Curcumin has been reported to inhibit cell growth and induce apoptosis in oral cancer cells. Although many studies have been done to uncover the mechanisms by which curcumin exerts its antitumor activity, the precise molecular mechanisms remain to be unclear. In the present study, we assessed the effects of curcumin on cell viability and apoptosis in oral cancer. For mechanistic studies, we used multiple cellular and molecular approaches such as gene transfection, real-time RT-PCR, Western blotting, invasion assay, and ELISA. For the first time, we found a significant reduction in cell viability in curcumin-treated cells, which was consistent with induction of apoptosis and also associated with down-regulation of Notch-1 and nuclear factor-κB (NF-κB). Taken together, we conclude that the down-regulation of Notch-1 by curcumin could be an effective approach, which will cause down-regulation of NF-κB, resulting in the inhibition of cell growth and invasion. These results suggest that antitumor activity of curcumin is mediated through a novel mechanism involving inactivation of Notch-1 and NF-κB signaling pathways.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • RNA Interference
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Time Factors
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • NOTCH1 protein, human
  • Receptor, Notch1
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 9
  • Curcumin