Curcumin impairs tumor suppressor p53 function in colon cancer cells

Carcinogenesis. 2004 Sep;25(9):1611-7. doi: 10.1093/carcin/bgh163. Epub 2004 Apr 16.


Curcumin (diferuloylmethane) is being considered as a potential chemopreventive agent in humans. In vitro it inhibits transcription by NF-kappaB, and the activity of lipoxygenase or cyclooxygenase enzymes, which facilitate tumor progression. In vivo it is protective in rodent models of chemical carcinogenesis. Curcumin contains an alpha,beta-unsaturated ketone, a reactive chemical substituent that is responsible for its repression of NF-kappaB. In compounds other than curcumin this same electrophilic moiety is associated with inactivation of the tumor suppressor, p53. Here we report that curcumin behaves analogously to these compounds. It disrupts the conformation of the p53 protein required for its serine phosphorylation, its binding to DNA, its transactivation of p53-responsive genes and p53-mediated cell cycle arrest.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Cycle
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Curcumin / pharmacology*
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Profiling
  • Genes, Tumor Suppressor / drug effects*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • Protein Binding
  • Protein Conformation / drug effects*
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / metabolism


  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Tumor Suppressor Protein p53
  • DNA
  • Curcumin