Epigallocatechin-3-gallate Inhibits the PDGF-induced VEGF Expression in Human Vascular Smooth Muscle Cells via Blocking PDGF Receptor and Erk-1/2

Int J Oncol. 2006 Nov;29(5):1247-52.

Abstract

Platelet-derived growth factor (PDGF) has been known to induce vascular endothelial growth factor (VEGF) expression in human vascular smooth muscle cells (hVSMCs). We previously reported that Erk-1/2 and AP-1 pathways are crucial in the PDGF-induced VEGF expression in hVSMCs . In this study, we investigated the effect of epigallocatechin-3-gallate (EGCG), the major green tea catechin, on the PDGF-induced VEGF expression in hVSMCs and the underlying mechanisms. EGCG were found to inhibit dose-dependently the VEGF expression and activation of PDGF receptor, Erk-1/2 and AP-1 induced by PDGF. In addition, cell free studies demonstrated that EGCG could directly inhibit the Erk-1/2 activity. Conditioned media from the hVSMCs treated with PDGF could remarkably stimulate the in vitro growth of human umbilical vein endothelial cells (HUVECs) but the media from the EGCG-pretreated hVSMCs lost its stimulatory activity for HUVEC proliferation. These results suggest that EGCG may exert the anti-angiogenic effect by inhibiting the PDGF-induced VEGF expression at multiple signaling levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Anticarcinogenic Agents / pharmacology*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Proliferation / drug effects
  • Culture Media, Conditioned / pharmacology
  • Endothelial Cells / drug effects
  • Humans
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • Platelet-Derived Growth Factor / antagonists & inhibitors
  • Platelet-Derived Growth Factor / pharmacology
  • Promoter Regions, Genetic / drug effects
  • Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors
  • Umbilical Cord / cytology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Angiogenesis Inhibitors
  • Anticarcinogenic Agents
  • Culture Media, Conditioned
  • Platelet-Derived Growth Factor
  • Vascular Endothelial Growth Factor A
  • Catechin
  • epigallocatechin gallate
  • Receptors, Platelet-Derived Growth Factor
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3