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MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom, inhibits tumor cells adhesion and migration.
- Source :
-
Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2009 May; Vol. 28 (4), pp. 188-93. Date of Electronic Publication: 2009 Apr 05. - Publication Year :
- 2009
-
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 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.
- Subjects :
- Amino Acid Sequence
Animals
Antigens, Neoplasm
Antineoplastic Agents chemistry
Antineoplastic Agents isolation & purification
Catalytic Domain drug effects
Cell Adhesion drug effects
Cell Line, Tumor drug effects
Cell Movement drug effects
Drug Screening Assays, Antitumor
Fibrosarcoma pathology
Humans
Integrin alpha5beta1 antagonists & inhibitors
Integrin alphaVbeta3 antagonists & inhibitors
Integrins antagonists & inhibitors
Melanoma pathology
Molecular Sequence Data
Neoplasm Proteins antagonists & inhibitors
Phospholipases A2 chemistry
Phospholipases A2 isolation & purification
Sequence Alignment
Sequence Homology, Amino Acid
Structure-Activity Relationship
Viper Venoms chemistry
Viper Venoms isolation & purification
Viper Venoms pharmacology
Antineoplastic Agents pharmacology
Phospholipases A2 pharmacology
Viper Venoms enzymology
Viperidae metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1569-1802
- Volume :
- 28
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Matrix biology : journal of the International Society for Matrix Biology
- Publication Type :
- Academic Journal
- Accession number :
- 19351557
- Full Text :
- https://doi.org/10.1016/j.matbio.2009.03.007