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.

Figure 1

Milestones in PLA₂ enzyme research. (1) Heinrikson et al. [81], (2) Lambeau et al. [56], (3) Maraganore et al. [10], (4) Lambeau et al. [82], (5) Landucci et al. [83], (6) Zouari-Kessenti et al. [21], Bazaa et al. [27], and (7) [27, 28].

Figure 2

Sequence alignment of Tunisian Viperidae sPLA₂: CC-PLA₂-1 (ACO92622) [28], CC-PLA₂-2 (ACO92623) [28], and MVL-PLA₂ (CAR40186) [26]. Gaps (—) have been introduced to optimize alignment.

Figure 3

(a) Tertiary model structure of CC-PLA₂-1 (pink), CC-PLA₂-2 (yellow), and MVL-PLA₂ (green). (b) Superimposition of the structural models of CC-PLA₂-1, CC-PLA₂-2, and MVL-PLA₂. The hypothetical integrin-binding loop (blue) is presented in each PLA₂.