MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom,inhibits tumor cells adhesion and migration |
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Authors: | Amine Bazaa José Luis Najet Srairi-Abid Olfa Kallech-Ziri Raoudha Kessentini-Zouari Céline Defilles Jean-Claude Lissitzky Mohamed El Ayeb Naziha Marrakchi |
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Affiliation: | 1. Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunisia;2. INSERM UMR 911-CRO2, Aix-Marseille Université, Marseille, France;3. Department of Biochemistry Faculty of Medicine of Tunis, Tunisia |
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Abstract: | 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 μM 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 α5β1 and αv-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. |
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