LAUSR

ABSTRACT In a previous study, we purified Sm‐PLGV an heterodimeric phospholipase A2, from the venom glands of the Tunisian scorpion Scorpio maurus. This enzyme contains a Long chain, a penta‐peptide insertion, which is cut out during the maturation process, followed by a short chain. A disulfide bridge links the two chains. Three recombinant forms of this enzyme were produced in Escherichia coli: rPLA2(+5) with a penta‐peptide insert, rPLA2(‐5) without the penta‐peptide, and the Long chain alone without the short one. In the present study, we showed that Sm‐PLGV, rPLA2(+5) and rPLA2(‐5) displayed more potent anti‐angiogenic activity in vitro than the recombinant Long chain and the short one obtained by chemical synthesis. These phospholipases A2 inhibited in a dose‐dependent manner adhesion, migration and invasion of Human Umbilical Vein Endothelial Cells. Using Matrigel™, we demonstrated that Sm‐PLGV, rPLA2(+5) and rPLA2(‐5) significantly inhibited tubulogensesis. We also showed a clear dissociation between the anti‐angiogenic effect of Sm‐PLGV and its catalytic activity. HighlightsSm‐PLGV is heterodimeric‐secreted phospholipase A2 purified from Scorpio maurus venom glands.Recombinant phospholipases rPLA2(+5) and rPLA2(‐5) inhibited angiogenesis more than the recombinant Long chain.Sm‐PLGV, rPLA2(+5) and rPLA2(‐5) inhibited HUVEC cells adhesion, migration and invasion.There is a dissociation between the anti‐angiogenic effect and the enzymatic activity.Sm‐PLGV tridimensional structure was not involved in its anti‐angiogenic activity.