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Cheiradone: a vascular endothelial cell growth factor receptor antagonist

Hussain, Sajjad; Slevin, Mark; Mesaik, Mohammad A.; Choudhary, Mohammad I.; Elosta, Abdul H.; Matou, Sabine; Ahmed, Nessar; West, David and Gaffney, John (2008) Cheiradone: a vascular endothelial cell growth factor receptor antagonist. BMC Cell Biology, 9 . Article Number: 7. ISSN 1471-2121

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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 VEGFstimulated 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 μM 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 μM 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.

Item Type:Article
Additional Information:Published: 29 January 2008. 10 pages (page numbers not for citation purposes).
Uncontrolled Keywords:Angiogenesis; physiological; pathological; Vascular endothelial growth factor; VEGF; fibroblast growth factor-2; FGF-2; Euphorbia species
Subjects:Q Science > Q Science (General)
Q Science > QH Natural history > QH301 Biology
Departments, Research Centres and Related Units:Academic Faculties, Institutes and Research Centres > Faculty of Science > Department of Biological Sciences
DOI:10.1186/1471-2121-9-7
Publisher's Statement:© 2008 Hussain et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Refereed:Yes
Status:Published
ID Code:663
Deposited On:04 Jun 2008 16:00
Last Modified:24 Feb 2012 15:19

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