Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up-regulating cyclin-dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53

Int J Oncol. 2002 Aug;21(2):379-83.

Abstract

To elucidate possible mechanisms of anti-angiogenic activity by curcumin, we performed cDNA microarray and found that curcumin modulated cell cycle related gene expression. For further confirmation, DNA contents and expression levels of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CDKIs) were examined by FACS analysis and Western blotting, respectively. Curcumin was found to induce G0/G1 and/or G2/M phase cell cycle arrest, up-regulate CDKIs, p21WAF1/CIP1, p27KIP1, and p53, and slightly down-regulate cyclin B1 and cdc2 in ECV304 cells. However, expression level of other cyclins and CDKs were not changed by curcumin. We, therefore, conclude that the up-regulation of CDKIs by curcumin plays a critical role in the regulation of cell cycle distribution in these cells, which may have a major role in anti-angiogenic activity of curcumin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Cell Cycle / drug effects*
  • Cell Cycle Proteins / metabolism*
  • Cell Division / drug effects
  • Curcumin / pharmacology*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclins / metabolism*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins / metabolism*
  • Umbilical Veins
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases
  • Curcumin