MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom, inhibits tumor cells adhesion and migration.
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.
Bazaa
Amine
A
Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur Belvedère BP74, Tunis, Tunisia. amine.bazaa@gmail.com
Luis
José
J
Srairi-Abid
Najet
N
Kallech-Ziri
Olfa
O
Kessentini-Zouari
Raoudha
R
Defilles
Céline
C
Lissitzky
Jean-Claude
JC
El Ayeb
Mohamed
M
Marrakchi
Naziha
N
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020134:Catalytic Domain / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005354:Fibrosarcoma / Q000473:pathology; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors; D016023:Integrins / Q000037:antagonists & inhibitors; D008545:Melanoma / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D054467:Phospholipases A2 / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014757:Viper Venoms / Q000737:chemistry / Q000201:enzymology* / Q000302:isolation & purification / Q000494:pharmacology; D017819:Viperidae / Q000378:metabolism*
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D016023:Integrins; D009363:Neoplasm Proteins; D014757:Viper Venoms; C073878:integrin alphavbeta6; C543741:MVL-PLA2, Macrovipera lebetina; D054467:Phospholipases A2