Epigallocatechin-3-gallate inhibits basic fibroblast growth factor-induced intracellular signaling transduction pathway in rat aortic smooth muscle cells

J Cardiovasc Pharmacol. 2002 Feb;39(2):271-7. doi: 10.1097/00005344-200202000-00014.

Abstract

Daily green tea drinking showed preventive effects on the progression of atherosclerosis. Although epigallocatechin-3-gallate [EGCG] has anti-proliferative effects on various cells, relatively little is known about the molecular mechanisms of the anti-proliferative effects of EGCG. To determine whether the transduction signals and protooncogene expression were affected by EGCG, this study investigated the molecular mechanism of the anti-proliferative effects in basic fibroblast growth factor (bFGF)-stimulated rat aortic smooth muscle cells (RAoSMCs). EGCG inhibited the proliferative response stimulated by 10% fetal bovine serum dose dependently in RAoSMCs (median inhibitory concentration [IC50]: 28.4 x 10(-6) M ). EGCG also inhibited the migration of bFGF-stimulated RAoSMCs in a dose-dependent manner, showing that 21.8 x 10(-6) M of EGCG significantly inhibited the migration by 75 +/- 5% in comparison with bFGF-stimulated migration. In RAoSMCs, EGCG dramatically inhibited Ras activation and c-jun N-terminal kinase (JNK) activity without affecting protein kinase C expression. Induction of c-jun mRNA stimulated by bFGF was significantly reduced dose dependently up to 87.3 x 10(-6) M of EGCG. These results indicate that the anti-proliferative effect of EGCG on RAoSMCs is partly Ras/JNK mediated, independent of protein kinase C, and is attributable to the downregulation of c-jun expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Aorta, Thoracic / cytology
  • Aorta, Thoracic / metabolism
  • Blotting, Western
  • Catechin / analogs & derivatives
  • Catechin / pharmacology*
  • Cell Division / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Down-Regulation
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblast Growth Factor 2 / physiology*
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscle, Smooth / cytology
  • Muscle, Smooth / metabolism*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • RNA, Messenger
  • Fibroblast Growth Factor 2
  • Catechin
  • epigallocatechin gallate
  • Protein Kinase C
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • ras Proteins