Wogonin suppresses tumor growth in vivo and VEGF-induced angiogenesis through inhibiting tyrosine phosphorylation of VEGFR2

Life Sci. 2008 Apr 23;82(17-18):956-63. doi: 10.1016/j.lfs.2008.02.013. Epub 2008 Mar 4.

Abstract

Previous studies revealed that wogonin, a naturally occurring monoflavonoid extracted from Scutellariae radix, possessed anticancer activity both in vitro and in vivo. However, the molecular mechanism of its potent anticancer activity remains poorly understood and warrants further investigations. In this study, we found for the first time that wogonin inhibited the growth and tumor angiogenesis of human gastric carcinoma in nude mice. We explored the inhibitory effect of wogonin on angiogenesis stimulated by vascular endothelial growth factor (VEGF) in vitro. Wogonin suppressed the VEGF-stimulated migration and tube formation of human umbilical vein endothelial cells (HUVECs). It also restrained VEGF-induced tyrosine phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2). This inhibition of receptor phosphorylation was correlated with a significant decrease in VEGF-triggered phosphorylated forms of ERK, AKT and p38. Taken together, these findings strongly suggest that wogonin might be a promising antitumor drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Blotting, Western
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Flavanones / pharmacology*
  • Free Radical Scavengers / pharmacology*
  • Immunohistochemistry
  • Mice
  • Mice, Nude
  • Microtubules / drug effects
  • Neoplasm Transplantation
  • Neovascularization, Physiologic / drug effects*
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects
  • Tyrosine / metabolism*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / pharmacology*
  • Vascular Endothelial Growth Factor Receptor-2 / drug effects
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Phytogenic
  • Flavanones
  • Free Radical Scavengers
  • Vascular Endothelial Growth Factor A
  • Tyrosine
  • Vascular Endothelial Growth Factor Receptor-2
  • p38 Mitogen-Activated Protein Kinases
  • wogonin