Macrovipera lebetinus obtusa Venom and Its Fractions Affect Human Dermal Microvascular Endothelial and Fibrosarcoma Cells.

The venom of Macrovipera lebetinus obtusa (MLO) has remarkable properties that are hard to overlook. This venom's described 38 protein components work synergistically, forming complexes that greatly enhance their combined effectiveness. Previous studies have shown that both crude venom and one of its components, obtustatin, can reduce sarcoma tumors by 50% and 30%, respectively. Obtustatin, a member of the short disintegrin family, inhibits the angiogenic activity of α1β1 integrin, the adhesive receptor of collagen IV. However, the mechanisms of the greater efficacy of the crude venom compared to its isolated components remain unclear. To investigate this, we propose an experimental work to explore the activity of certain low-molecular-weight components of MLO venom. Our in vitro tests on fibrosarcoma (HT-1080) cells using six venom fractions revealed cytotoxic fractions, which, through mass spectrometry, were identified as containing protein classes such as dimeric and short disintegrins, acidic phospholipase A2, and serine proteinases. Notably, these fractions exhibited minimal toxicity to human dermal microvascular endothelial (HDEC) cells, suggesting their potential as a promising candidate for oncotherapy in the future.