School of Pharmacy, Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Toxins (Basel). 2012 Oct;4(10):862-77. doi: 10.3390/toxins4100862. Epub 2012 Oct 18.
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.
一种 C 型凝集素样蛋白（CTL），最初被鉴定为 VP12，最近被命名为 Vixapatin，从以色列毒蛇 Vipera xantina palestinae 蛇毒中分离并鉴定出来。这种 CTL 被鉴定为一种选择性的 α2β1 整合素抑制剂，具有抗黑色素瘤转移活性。本研究的主要目的是证明这种蛋白也是一种有效的新型抗血管生成化合物的可能性。通过粘附实验，我们证明 Vixapatin 选择性地、有效地抑制了 K562 过表达细胞中 α2 介导的粘附，IC50 为 3 nM。3 nM 的 Vixapatin 阻断了人真皮微血管内皮细胞（HDMEC）的增殖；25 nM 抑制了人纤维肉瘤 HT-1080 细胞胶原 I 诱导的迁移；50 nM 的大鼠 C6 神经胶质瘤和人乳腺癌 MDA-MB-231 细胞。1 μM 的 Vixapatin 在 Matrigel 实验中使 HDMEC 管形成减少了 75%。此外，在无壳鸡胚绒毛尿囊膜试验中，1 μM 的 Vixapatin 减少了 bFGF 诱导的生理性血管生成的 70%，减少了 C6 神经胶质瘤诱导的病理性血管生成的 94%。Vixapatin 抑制血管生成过程的所有步骤的能力表明，它是一种研究 α2β1 整合素介导的血管生成的新型药理学工具，也是开发新型抗血管生成/血管稳定/抗癌药物的先导化合物。
