A New Protein Extract Inhibitor from Hypobranchial Purple Gland of Hexaplex trunculus, a Mediterranean Mollusk, Impairs the Motility of Human Glioblastoma U87 and the HeLa Cell Line of Cervical Carcinoma Cells.

The aim of this study is to evaluate the effect of hypobranchial gland protein extracts (HGPEs) of Hexaplex trunculus on the viability, cell adhesion, and migration of human U87 glioblastoma cells and the HeLa cell line obtained from epithelial cervical carcinoma cells. Analysis of the HGPE on polyacrylamide gel (12%) shows a variety of proteins whose molecular weights vary between 12 and 1OO kDa. Chromatographic analysis shows 16 peaks obtained at various retention times. Cytotoxic effect was observed after 24 hours of incubation at the concentrations 20, 40, and 60 µg/ml in a dose-dependent manner. Concentrations giving 50% inhibition (IC50) are 22 µg/ml for U87 and 15 µg/ml for HeLa cells. Our results show inhibition of U87 and HeLa cancer cell adhesion at concentrations of 10 and 20 µg/ml, respectively. High-pressure liquid chromatography fractions did not show antiadhesive effect on both cancer cell lines. The presence of HGPEs completely blocked the migration of the two cancer cell lines at 10 µg/ml. This inhibition is dose-dependent. IC50 is about 2.5 µg/ml for both cancer cells. The HGPE of Hexaplex trunculus may have the potential to serve as a model for future anticancer drug development with probably a synergistic activity of the proteins of this extract.

Lebestatin, a disintegrin from Macrovipera venom, inhibits integrin-mediated cell adhesion, migration and angiogenesis.

Lebestatin, a new member of the lysine-threonine-serine (KTS)-disintegrin family, was purified to homogeneity from Tunisian snake (Macrovipera lebetina) venom. It is a single-chain polypeptide composed of 41 amino acids. The amino-acid sequence of lebestatin shows that it displays a pattern of cysteines similar to other short disintegrins, but contains the sequence KTS rather than RGD in its integrin-binding loop. Lebestatin presents a high homology with obtustatin and viperistatin. Lebestatin interacts specifically with the alpha1beta1 integrin. It was thus able to inhibit both adhesion and migration of PC12 and alpha1beta1 integrin-expressing CHO cells (CHO-alpha1) to type I and IV collagens. This disintegrin also affected adhesion and migration of endothelial cells and exhibited an anti-angiogenic effect in vivo when using the 8-day-old embryo chick chorioallantoic membrane model.