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.
Keywords: C-type lectin protein; Vixapatin (VP12); α2β1; integrin; adhesion; migration; tube formation; Matrigel; CAM assay; angiogenesis
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Momic, T.; Cohen, G.; Reich, R.; Arlinghaus, F.T.; Eble, J.A.; Marcinkiewicz, C.; Lazarovici, P. Vixapatin (VP12), a C-Type Lectin-Protein from Vipera xantina palestinae Venom: Characterization as a Novel Anti-angiogenic Compound. Toxins 2012, 4, 862-877.
Momic T, Cohen G, Reich R, Arlinghaus FT, Eble JA, Marcinkiewicz C, Lazarovici P. Vixapatin (VP12), a C-Type Lectin-Protein from Vipera xantina palestinae Venom: Characterization as a Novel Anti-angiogenic Compound. Toxins. 2012; 4(10):862-877.
Momic, Tatjana; Cohen, Gadi; Reich, Reuven; Arlinghaus, Franziska T.; Eble, Johannes A.; Marcinkiewicz, Cezary; Lazarovici, Philip. 2012. "Vixapatin (VP12), a C-Type Lectin-Protein from Vipera xantina palestinae Venom: Characterization as a Novel Anti-angiogenic Compound." Toxins 4, no. 10: 862-877.