期刊
TOXINS
卷 4, 期 10, 页码 862-877出版社
MDPI
DOI: 10.3390/toxins4100862
关键词
C-type lectin protein; Vixapatin (VP12); alpha 2 beta 1; integrin; adhesion; migration; tube formation; Matrigel; CAM assay; angiogenesis
资金
- David R. Bloom Center for Pharmacy
- Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem, Israel
- German-Israeli Foundation [GIF-994-3.9/2008]
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 alpha 2 beta 1 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 alpha 2 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 mu M Vixapatin reduced HDMEC tube formation by 75% in a Matrigel assay. Furthermore, 1 mu M 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 alpha 2 beta 1 integrin mediated angiogenesis and a lead compound for the development of a novel anti-angiogenic/angiostatic/anti-cancer drug.
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