title: Vixapatin (VP12), a c-type lectin-protein from Vipera xantina palestinae venom: characterization as a novel anti-angiogenic compound.
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 IC(50) 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.
authors.affiliation: School of Pharmacy, Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel. momict@gmail.com
authors.forename: Tatjana
authors.initials: T
authors.lastname: Momic
authors.forename: Gadi
authors.initials: G
authors.lastname: Cohen
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
authors.forename: Franziska T
authors.initials: FT
authors.lastname: Arlinghaus
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Eble
authors.forename: Cezary
authors.initials: C
authors.lastname: Marcinkiewicz
authors.forename: Philip
authors.initials: P
authors.lastname: Lazarovici
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D049033:Chorioallantoic Membrane / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D038982:Integrin alpha2beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020014:K562 Cells; D037181:Lectins, C-Type / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D014757:Viper Venoms / Q000494:pharmacology*; D017819:Viperidae
chemical_list: D020533:Angiogenesis Inhibitors; D038982:Integrin alpha2beta1; D037181:Lectins, C-Type; D014757:Viper Venoms; C075104:Angiostat; D003094:Collagen