Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression

Cancer Biol Ther. 2009 Jul;8(14):1360-8. doi: 10.4161/cbt.8.14.8720. Epub 2009 Jul 13.

Abstract

Curcumin (diferuloylmethane), is a natural chemopreventive agent known to inhibit the proliferation of several cancer cell lines. It has been previously demonstrated that curcumin is a potent inhibitor of EGF-receptor (EGFR) tyrosine kinase, but its inhibitive effect on p21-activated kinase 1 (PAK1), a downstream protein of EGFR, has not been defined. In this paper we found that curcumin repressed the expression of HER2 and inhibited the kinase activity of PAK1 without affecting its expression. Silencing HER2 in gastric cancer cells showed that even if PAK1 activity was transiently strengthened by EGF, curcumin still had a strong inhibitive effect. It should be emphasized that kinase assay in vitro showed that curcumin could act as an ATP-competitive inhibitor, which was supported by computer-aided molecular modeling. Curcumin also downregulated the mRNA and the protein expression of cyclin D1 and suppressed transition of the cells from G(1) to S phase. Therefore, curcumin inhibited the proliferation and invasion of gastric cancer cells. Overall, these results provided novel insights into the mechanisms of curcumin inhibition of gastric cancer cell growth and potential therapeutic strategies for gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Anticarcinogenic Agents / pharmacology*
  • Cell Division / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / enzymology
  • Cell Line, Tumor / pathology
  • Curcumin / pharmacology*
  • Cyclin D1 / biosynthesis*
  • Cyclin D1 / genetics
  • Down-Regulation / drug effects
  • Drug Screening Assays, Antitumor
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, erbB-2 / drug effects
  • Humans
  • Neoplasm Invasiveness / prevention & control
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Protein Kinase Inhibitors / pharmacology*
  • Receptor, ErbB-2 / biosynthesis
  • Stomach Neoplasms / pathology*
  • p21-Activated Kinases / biosynthesis*
  • p21-Activated Kinases / genetics

Substances

  • Anticarcinogenic Agents
  • CCND1 protein, human
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Cyclin D1
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • PAK1 protein, human
  • p21-Activated Kinases
  • Curcumin