Two purified and characterized phospholipases A2 from Cerastes cerastes venom, that inhibit cancerous cell adhesion and migration.
Two non-toxic PLA2s were purified to homogeneity from Cerastes cerastes Tunisian snake venom. The purification process employed gel filtration on Sephadex G-75 followed by C18 reverse phase high-pressure liquid chromatography. These two acidic enzymes, namely CC-PLA2-1 and CC-PLA2-2, have a molecular weight of 13,737.52 and 13,705.63 Da, respectively. These two PLA2 are the first reported glycosylated phospholipases A2 purified from snake venom. The rates of glycosylation are 2.5% and 0.5% (w/w), respectively. Specific activities of 1800 U/mg and 2400 U/mg for CC-PLA2-1 and CC-PLA2-2, respectively, were measured at optimal conditions. CC-PLA2-1 and CC-PLA2-2 strongly inhibited coagulation. They also exhibited a marked dose-dependent inhibitory effect on platelet aggregation induced by ADP and arachidonic acid in platelet-rich plasma. Interestingly, CC-PLA2-1 and CC-PLA2-2 inhibited in a dose-dependent manner adhesion of IGR39 melanoma and HT1080 fibrosarcoma cells to fibrinogen and fibronectin. Furthermore, both CC-PLA2-1 and CC-PLA2-2 abolished HT1080 cell migration towards fibrinogen and fibronectin. This activity is reported for the first time for PLA2 enzymes.
Zouari-Kessentini
Raoudha
R
Laboramtoire des Venins et Toxines, Institut Pasteur de Tunis, 13 Place Pasteur, BP.74, 1002 Tunis Belvédère, Tunisia. zouari_raoudha@yahoo.fr
Luis
José
J
Karray
Aida
A
Kallech-Ziri
Olfa
O
Srairi-Abid
Najet
N
Bazaa
Amine
A
Loret
Erwann
E
Bezzine
Sofiane
S
El Ayeb
Mohamed
M
Marrakchi
Naziha
N
D000595:Amino Acid Sequence; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D054467:Phospholipases A2 / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D014757:Viper Venoms / Q000737:chemistry / Q000201:enzymology*; D017819:Viperidae / Q000502:physiology*
D014757:Viper Venoms; D054467:Phospholipases A2