Antitumoral Potential of Tunisian Snake Venoms Secreted Phospholipases A₂

Abstract

Phospholipases type A2 (PLA2s) are the most abundant proteins found in Viperidae snake venom. They are quite fascinating from both a biological and structural point of view. Despite similarity in their structures and common catalytic properties, they exhibit a wide spectrum of pharmacological activities. Besides being hydrolases, secreted phospholipases A2 (sPLA2) are an important group of toxins, whose action at the molecular level is still a matter of debate. These proteins can display toxic effects by different mechanisms. In addition to neurotoxicity, myotoxicity, hemolytic activity, antibacterial, anticoagulant, and antiplatelet effects, some venom PLA2s show antitumor and antiangiogenic activities by mechanisms independent of their enzymatic activity. This paper aims to discuss original finding against anti-tumor and anti-angiogenic activities of sPLA2 isolated from Tunisian vipers: Cerastes cerastes and Macrovipera lebetina, representing new tools to target specific integrins, mainly, α5β1 and αv integrins.

Biological characterization of the Amazon coral Micrurus spixii snake venom: Isolation of a new neurotoxic phospholipase A2

“…Several studies were done with human leukemic T cell lines (JURKAT), tumoral cells from mice (EAT line), human melanoma (IGR39) and fibrosarcoma HT1080 (Costa et al, 2008;Zouari-Kessentini et al, 2013). It may be suggested, that phospholipase A 2 activity is directly correlated to antitumoral activity in elapid and viperid venoms, since this toxin is responsible for directly interfering with the mechanisms of angiogenesis, cell proliferation and inducing tumor regression by stimulating apoptotic mechanisms in tumor cells (Calderon et al, 2014;Rodrigues et al, 2009).…”

Anti-angiogenic activities of snake venom CRISP isolated from Echis carinatus sochureki

“…C-type lectins (CLPs) are another group of snake venom proteins regulate angiogenesis by binding to integrin receptors [8,9]. Snake venom phospholipases A2 are reportedly angiostatic compounds, as they bind to the RGD-dependent integrins on endothelial cells in a non-enzymatic manner [10]. In this paper we report that snake venom cysteine-rich secretory protein (CRISP) is also an anti-angiogenic protein that acts through interactions with endothelial cells.…”

Effect of the Montivipera bornmuelleri snake venom on human blood: coagulation disorders and hemolytic activities

“…Most snake venoms contain phospholipases that hydrolyze free or membrane phospholipids into fatty acids and lysophospholipids. Some of these PLA2 require Ca 2+ for their activity [4], that's why the hemolytic activity of M. bornmuelleri venom was tested in the presence of Ca 2+ at a concentration of 20 mM. Results obtained didn't differ from the previous one demonstrating that even in the presence of Ca 2+ , the hemolysis was similar or lower the negative control (data not shown).…”

“…The snake crude venom has a wide spectrum of biological activities, such as neurotoxic, cardiotoxic, cytotoxic and antibacterial activity [1][2][3]. Furthermore, some viper venom components show antitumor and antiangiogenic activities [4]. Due to this broad range of biological functions, the snake venom and its bioactive components have been the subject of many scientific articles in different research fields, including biochemistry, biophysics, toxicology, pharmacology and medicine [1,[5][6][7].…”