Cheiradone: a vascular endothelial cell growth factor receptor antagonist

BMC Cell Biol. 2008 Jan 29;9:7. doi: 10.1186/1471-2121-9-7.

Abstract

Background: Angiogenesis, the growth of new blood vessels from the pre-existing vasculature is associated with physiological (for example wound healing) and pathological conditions (tumour development). Vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) are the major angiogenic regulators. We have identified a natural product (cheiradone) isolated from a Euphorbia species which inhibited in vivo and in vitro VEGF- stimulated angiogenesis but had no effect on FGF-2 or EGF activity. Two primary cultures, bovine aortic and human dermal endothelial cells were used in in vitro (proliferation, wound healing, invasion in Matrigel and tube formation) and in vivo (the chick chorioallantoic membrane) models of angiogenesis in the presence of growth factors and cheiradone. In all cases, the concentration of cheiradone which caused 50% inhibition (IC50) was determined. The effect of cheiradone on the binding of growth factors to their receptors was also investigated.

Results: Cheiradone inhibited all stages of VEGF-induced angiogenesis with IC50 values in the range 5.20-7.50 microM but did not inhibit FGF-2 or EGF-induced angiogenesis. It also inhibited VEGF binding to VEGF receptor-1 and 2 with IC50 values of 2.9 and 0.61 microM respectively.

Conclusion: Cheiradone inhibited VEGF-induced angiogenesis by binding to VEGF receptors -1 and -2 and may be a useful investigative tool to study the specific contribution of VEGF to angiogenesis and may have therapeutic potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors
  • Animals
  • Cattle
  • Cell Differentiation
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply
  • Chorioallantoic Membrane / drug effects
  • Collagen
  • Diterpenes / pharmacology*
  • Drug Combinations
  • Endothelial Cells / drug effects*
  • Endothelial Cells / pathology
  • Endothelial Cells / physiology
  • Epidermal Growth Factor / metabolism
  • Euphorbia*
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Laminin
  • Neoplasm Invasiveness / prevention & control
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Physiologic / drug effects*
  • Phytotherapy*
  • Plant Preparations / pharmacology*
  • Plant Preparations / therapeutic use
  • Proteoglycans
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Wound Healing / drug effects

Substances

  • Angiogenesis Inhibitors
  • Diterpenes
  • Drug Combinations
  • Laminin
  • Plant Preparations
  • Proteoglycans
  • cheiradone
  • Fibroblast Growth Factor 2
  • matrigel
  • Epidermal Growth Factor
  • Collagen
  • Receptors, Vascular Endothelial Growth Factor