Abstract

Macrovipera lebetina obtusa (MLO) is a venomous snake endemic to Middle East. Here we describe the therapeutic potential of the MLO snake venom. In S-180 sarcoma-bearing mouse model, we showed that the MLO snake venom inhibits tumour growth by 50%. In human dermal microvascular endothelial cells (HMVEC-D), treatment with the MLO snake venom lead to an increase of expression levels of the vascular endothelial growth factor (VEGF), while the level of the expression of caspase 8 did not change. In HMVEC-D cells MLO snake venom induces necroptosis, rather than apoptosis. In the chick embryo chorioallantoic membrane (CAM) assay, exposure to MLO snake venom inhibited bFGF-induced angiogenesis by 22%. Taken together, these results indicate that the MLO snake venom has a potent cytotoxic activity. Regulated necroptic cell death pathway, which is engaged by MLO snake venom, may become a promising novel target for antitumor therapies.

中文翻译：

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Macrovipera lebetina obtusa蛇毒作为S-180肉瘤小鼠模型中抗肿瘤作用的调节剂

摘要

大叶紫菜（MLO）是中东地区特有的毒蛇。在这里，我们描述了MLO蛇毒的治疗潜力。在具有S-180肉瘤的小鼠模型中，我们显示MLO蛇毒可抑制肿瘤生长50％。在人类真皮微血管内皮细胞（HMVEC-D）中，用MLO蛇毒进行处理可导致血管内皮生长因子（VEGF）的表达水平增加，而caspase 8的表达水平却没有变化。在HMVEC-D细胞中，MLO蛇毒会导致坏死，而不是凋亡。在鸡胚绒膜尿囊膜（CAM）分析中，暴露于MLO蛇毒可抑制bFGF诱导的血管生成22％。综上所述，这些结果表明MLO蛇毒具有有效的细胞毒活性。MLO蛇毒参与的调节性坏死细胞死亡途径，