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 mu M 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 mu M 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.