Cheiradone

A vascular endothelial cell growth factor receptor antagonist

Sajjad Hussain, Mark Slevin, Osman Mesaik Mohammed Ahmed Hassan, Mohammad I. Choudhary, Abdul H. Elosta, Sabine Matou, Nessar Ahmed, David West, John Gaffney

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 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.

Original languageEnglish
Article number7
JournalBMC Cell Biology
Volume9
DOIs
Publication statusPublished - 29 Oct 2008
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor
Vascular Endothelial Growth Factor A
Fibroblast Growth Factor 2
Epidermal Growth Factor
Inhibitory Concentration 50
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Wound Healing
Intercellular Signaling Peptides and Proteins
Euphorbia
Chorioallantoic Membrane
Biological Products
Blood Vessels
cheiradone
Endothelial Cells
Skin
Growth
Neoplasms

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hussain, S., Slevin, M., Mohammed Ahmed Hassan, O. M., Choudhary, M. I., Elosta, A. H., Matou, S., ... Gaffney, J. (2008). Cheiradone: A vascular endothelial cell growth factor receptor antagonist. BMC Cell Biology, 9, [7]. https://doi.org/10.1186/1471-2121-9-7

Cheiradone : A vascular endothelial cell growth factor receptor antagonist. / Hussain, Sajjad; Slevin, Mark; Mohammed Ahmed Hassan, Osman Mesaik; Choudhary, Mohammad I.; Elosta, Abdul H.; Matou, Sabine; Ahmed, Nessar; West, David; Gaffney, John.

In: BMC Cell Biology, Vol. 9, 7, 29.10.2008.

Research output: Contribution to journalArticle

Hussain, S, Slevin, M, Mohammed Ahmed Hassan, OM, Choudhary, MI, Elosta, AH, Matou, S, Ahmed, N, West, D & Gaffney, J 2008, 'Cheiradone: A vascular endothelial cell growth factor receptor antagonist', BMC Cell Biology, vol. 9, 7. https://doi.org/10.1186/1471-2121-9-7
Hussain, Sajjad ; Slevin, Mark ; Mohammed Ahmed Hassan, Osman Mesaik ; Choudhary, Mohammad I. ; Elosta, Abdul H. ; Matou, Sabine ; Ahmed, Nessar ; West, David ; Gaffney, John. / Cheiradone : A vascular endothelial cell growth factor receptor antagonist. In: BMC Cell Biology. 2008 ; Vol. 9.
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