KR-31831, benzopyran derivative, inhibits VEGF-induced angiogenesis of HUVECs through suppressing KDR expression

Int J Oncol. 2008 Jun;32(6):1311-5. doi: 10.3892/ijo_32_6_1311.

Abstract

Angiogenesis is important in the development and progression of cancer, therefore the therapeutic approach based on anti-angiogenesis may represent a promising therapeutic option. KR-31831 is a novel anti-ischemic agent. Previously, we reported the anti-angiogenic activity of KR-31831. In the present study we investigated the molecular mechanisms underlying anti-angiogenic activity of KR-31831. We show that KR-31831 inhibits vascular endothelial growth factor (VEGF)-induced proliferation and tube formation via release of intracellular Ca2+ and phosphorylation of extra-cellular regulated kinase 1/2 (Erk 1/2) in human umbilical vein endothelial cells (HUVECs). Moreover, the expression of VEGF receptor 2 (VEGFR2, known as Flk-1 or KDR) was reduced by the treatment of KR-31831. These results suggest that KR-31831 may have inhibitory effects on tumor angiogenesis through down-regulation of KDR expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzopyrans / pharmacology*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Collagen / metabolism
  • Drug Combinations
  • Endothelium, Vascular / drug effects*
  • Humans
  • Imidazoles / pharmacology*
  • Immunoblotting
  • Laminin / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neovascularization, Pathologic / prevention & control*
  • Phosphorylation
  • Proteoglycans / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Umbilical Veins / cytology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / pharmacology
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*

Substances

  • Benzopyrans
  • Drug Combinations
  • Imidazoles
  • KR 31831
  • Laminin
  • Proteoglycans
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • matrigel
  • Collagen
  • Vascular Endothelial Growth Factor Receptor-2
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3