MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom, inhibits tumor cells adhesion and migration.

Amine Bazaa (1) , José Luis (2) , Najet Srairi-Abid (1) , Olfa Kallech-Ziri (1) , Raoudha Kessentini-Zouari (1) , Céline Defilles (2) , Jean-Claude Lissitzky (2) , Mohamed El Ayeb (1) , Naziha Marrakchi (1, 3)

1 Institut Pasteur de Tunis
2 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie
3 Faculté de Médecine de Tunis

Here, we report the purification and characterization of an acidic Asp49 phospholipase A2, named MVL-PLA2, with a molecular mass of 13,626.64 Da. The complete MVL-PLA2 cDNA was cloned from Macrovipera lebetina transmediterranea venom gland cDNA library. MVL-PLA2 possesses 122 amino acid residues, including 14 cysteines, and belongs to group II snake venom phospholipase A2 enzymes. MVL-PLA2 was not cytotoxic up to 2 muM and completely abolished cell adhesion and migration of various human tumor cells. Chemical modification with p-bromophenacyl bromide abolished the enzymatic activity of MVL-PLA2 without affecting its anti-tumor effect, suggesting the presence of 'pharmacological sites' distinct from the catalytic site in snake venom phospholipase A2. We demonstrated for the first time that the anti-tumor effect of MVL-PLA2 was mediated by alpha5beta1 and alphav-containing integrins. This finding may serve as starting point for structure-function relationship studies leading to design a new generation of specific anti-cancer drugs.

Amine Bazaa, José Luis, Najet Srairi-Abid, Olfa Kallech-Ziri, Raoudha Kessentini-Zouari, et al.. MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom, inhibits tumor cells adhesion and migration.. Matrix Biology, 2009, 28 (4), pp.188-93. ⟨10.1016/j.matbio.2009.03.007⟩. ⟨pasteur-00612541⟩