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Vol 55(2021) N 3 p. 405-412; DOI 10.1134/S0026893321020217  N. Ghazaryan1,2*, N. Movsisyan2,3, J.C. Macedo4, S. Vaz4, N. Ayvazyan1, L. Pardo2, E. Logarinho4 Macrovipera lebetina obtusa Snake Venom as a Modulator of Antitumor Effect in S-180 Sarcoma Mouse Model 1Laboratory of Toxinology and Molecular Systematics, Institute of Physiology, Yerevan, 0028 Armenia2Oncophysiology Group, Max Planck Institute for Experimental Medicine, Göttingen, 37075 Germany 3Göttingen Graduate School for Neurosciences, Biophysics, and Molecular Biosciences, Göttingen, 37075 Germany 4Aging and Aneuploidy Laboratory, Institute de Biologia Molecular e Celular, Instituto de Investigação e Inavação em Saúde - i3S, Universidade do Porto, Porto, 4200-135 Portugal *naringhazaryan@gmail.com Received - 2020-06-11; Revised - 2020-08-14; Accepted - 2020-08-17 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. snake venom, sarcoma, angiogenesis, necroptosis |
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