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

Autor: Raoudha Kessentini-Zouari, José Luis, Jean-Claude Lissitzky, Amine Bazaa, Mohamed El Ayeb, Céline Defilles, Olfa Kallech-Ziri, Najet Srairi-Abid, Naziha Marrakchi
Přispěvatelé: Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine de Tunis, Université de Tunis El Manar (UTM)
Jazyk: angličtina
Rok vydání: 2009
Předmět:
MESH: Neoplasm Proteins
Integrins
MESH: Sequence Homology
Amino Acid
Fibrosarcoma
MESH: Viperidae
MESH: Antigens
Neoplasm
MESH: Catalytic Domain
Venom
MESH: Amino Acid Sequence
MESH: Structure-Activity Relationship
Cell Movement
Catalytic Domain
Viperidae
MESH: Animals
Cytotoxicity
Melanoma
MESH: Phospholipases A2
MESH: Cell Movement
0303 health sciences
biology
MESH: Fibrosarcoma
030302 biochemistry & molecular biology
MESH: Drug Screening Assays
Antitumor
MESH: Integrins
Neoplasm Proteins
3. Good health
MESH: Integrin alphaVbeta3
Biochemistry
Snake venom
lipids (amino acids
peptides
and proteins)
MESH: Viper Venoms
Macrovipera lebetina
Integrin alpha5beta1
MESH: Cell Line
Tumor
MESH: Melanoma
Molecular Sequence Data
Integrin
MESH: Sequence Alignment
Antineoplastic Agents
Viper Venoms
MESH: Cell Adhesion
Structure-Activity Relationship
03 medical and health sciences
Phospholipase A2
Antigens
Neoplasm
Cell Line
Tumor
Cell Adhesion
Animals
Humans
Amino Acid Sequence
Cell adhesion
Molecular Biology
030304 developmental biology
MESH: Humans
MESH: Molecular Sequence Data
Sequence Homology
Amino Acid
MESH: Integrin alpha5beta1
cDNA library
Integrin alphaVbeta3
biology.organism_classification
Molecular biology
Phospholipases A2
biology.protein
MESH: Antineoplastic Agents
Drug Screening Assays
Antitumor
Sequence Alignment
Zdroj: Matrix Biology
Matrix Biology, Elsevier, 2009, 28 (4), pp.188-93. ⟨10.1016/j.matbio.2009.03.007⟩
ISSN: 0945-053X
DOI: 10.1016/j.matbio.2009.03.007⟩
Popis: 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.
Databáze: OpenAIRE
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