| Summary: | <p>Abstract</p> <p>Background</p> <p>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 <it>Euphorbia </it>species which inhibited <it>in vivo </it>and <it>in vitro </it>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 <it>in vitro </it>(proliferation, wound healing, invasion in Matrigel and tube formation) and <it>in vivo </it>(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 (IC<sub>50</sub>) was determined. The effect of cheiradone on the binding of growth factors to their receptors was also investigated.</p> <p>Results</p> <p>Cheiradone inhibited all stages of VEGF-induced angiogenesis with IC<sub>50 </sub>values in the range 5.20–7.50 μM but did not inhibit FGF-2 or EGF-induced angiogenesis. It also inhibited VEGF binding to VEGF receptor-1 and 2 with IC<sub>50 </sub>values of 2.9 and 0.61 μM respectively.</p> <p>Conclusion</p> <p>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.</p>
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