Abstract
A C-type lectin-like protein (CTL), originally identified as VP12 and lately named Vixapatin, was isolated and characterized from Israeli viper Vipera xantina palestinae snake venom. This CTL was characterized as a selective α2β1 integrin inhibitor with anti-melanoma metastatic activity. The major aim of the present study was to prove the possibility that this protein is also a potent novel anti-angiogenic compound. Using an adhesion assay, we demonstrated that Vixapatin selectively and potently inhibited the α2 mediated adhesion of K562 over-expressing cells, with IC50 of 3 nM. 3 nM Vixapatin blocked proliferation of human dermal microvascular endothelial cells (HDMEC); 25 nM inhibited collagen I induced migration of human fibrosarcoma HT-1080 cells; and 50 nM rat C6 glioma and human breast carcinoma MDA-MB-231 cells. 1 µM Vixapatin reduced HDMEC tube formation by 75% in a Matrigel assay. Furthermore, 1 µM Vixapatin decreased by 70% bFGF-induced physiological angiogenesis, and by 94% C6 glioma-induced pathological angiogenesis, in shell-less embryonic quail chorioallantoic membrane assay. Vixapatin’s ability to inhibit all steps of the angiogenesis process suggest that it is a novel pharmacological tool for studying α2β1 integrin mediated angiogenesis and a lead compound for the development of a novel anti-angiogenic/angiostatic/anti-cancer drug.
Highlights
Angiogenesis is a complex yet tightly regulated process involving proliferation, migration and capillary sprouting of vascular endothelial cells
In the present study we proved for the first time that Vixapatin is endowed with anti-angiogenic activity, paradigmatically representing an important novel property of this family of C-type lectin-like protein (CTL) antagonists of α2β1 integrin collagen receptor
Since α2β1 integrin is expressed in different tumors and enhances their angiogenesis [31,32] we investigated the effect of Vixapatin on several tumor cell lines
Summary
Angiogenesis is a complex yet tightly regulated process involving proliferation, migration and capillary sprouting of vascular endothelial cells. Angiogenesis is regulated by a variety of angiogenic growth factors, and ECM proteins and their cognate integrin receptors. The concept that angiogenesis is essential for tumor growth and metastasis has raised interest in the investigation of anti-angiogenic compounds targeting vascular endothelial cells [1]. Snake venoms have been used for purification of different pro-angiogenic [4] and anti-angiogenic [5] factors. These and other factors belong to two protein families—disintegrins [6]
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