[Snake venoms C-type lectins and their receptors on platelets and cancerous cells]. / Les lectines de type C de venins de serpents et leurs récepteurs sur les plaquettes et les cellules cancéreuses.

Snake venoms are a rich natural source of bioactive molecules, such as peptides, proteins and enzymes, more and more used in biomedical research in diagnostic or therapeutic purposes. The protein components of snake venoms belong to diverse families such as serine proteases, phospholipases, disintegrins, metalloproteinases and C-type lectins. Due to their effects on various receptors such as GPIb, GPVI, alpha2beta1..., the C-type lectins were considered, in first time, as modulators of the platelet aggregation. Recently, some of them have been described for their anti-tumoral potential effect due to their capacity to inhibit adhesion, migration, proliferation and invasion of different cancer cell lines. Also, the C-type lectins have a powerful antiangiogenic effect in vivo and in vitro by interacting with integrins of endothelial cells.

[Effect of Macrovipera lebetina and Cerastes cerastes venoms on adherence to integrins of cancerous cells (IGR39, HT29-D4 and IGROV1)]. / Effet des venins de Macrovipera lebetina et de Cerastes cerastes sur l'adherence aux intégrines des cellules cancéreuses (IGR39, HT29-D4 et IGROV1).

In this work, we provide experimental arguments in favor of the fact that components from Macrovipera lebetina and Cerastes cerastes venoms bind to IGR39 melanoma cells but not to HT29D4 cells that derive from carcinoma adenome. Furthermore, Macrovipera lebetina and Cerastes cerastes venoms inhibit the adherence of IGR39 and HT 29-D4 to various extracellular matrix proteins. Macrovipera lebetina and Cerastes cerastes venoms did not inhibit the non specific adherence of IGR 39 cells to polylysine. In addition, binding of components from Cerastes cerastes venom to IGR39 cells is inhibited by GRGDS peptide and by monoclonal antibidy anti-av, while these two components have no effect on the adherence of IGR39 to Macrovipera lebetina venom.

Lebecetin, a C-lectin protein from the venom of Macrovipera lebetina that inhibits platelet aggregation and adhesion of cancerous cells.

A novel C-lectin protein, lebecetin, was purified and characterized from the venom of Macrovipera lebetina. It is a disulfide-linked heterodimer of 15 and 16 kD. The subunits are homologous to each other and to the other snake venom proteins of the C-type (Ca(2+)-dependent) lectin superfamily. Lebecetin shows a potent inhibitory effect on whole blood and washed platelets induced by different agonists. It inhibits the agglutination of human fixed platelets in the presence of ristocetin. Lebecetin also interferes with the adhesion of IGR39 melanoma and HT29D4 adenocarcinoma cells. These two lines adhere to lebecetin used as matrix. Lebecetin is also able to strongly reduce IGR39 and HT29D4 cell adhesion to fibrinogen and laminin, but not to fibronectin and collagen types I and IV, respectively. Adhesion properties of lebecetin may thus involve integrin receptors.

Lebetin peptides: potent platelet aggregation inhibitors.

Lebetins from Macrovipera lebetina snake venom constitute a new class of inhibitors of platelet aggregation. There are two groups of peptides: lebetin 1 (L1; 11- to 13-mer) and lebetin 2 (L2; 37- to 38-mer). The short lebetins are identical to the N-terminal segments of the longer ones. They inhibit platelet aggregation induced by various agonists (e.g. thrombin, PAF-acether or collagen). The shortest lebetin (11-mer) shows potent inhibition of rabbit (IC(50) = 7 nM) and human (IC(50) = 5 nM) platelets. They prevent collagen-induced thrombocytopenia in rats. N- and C-terminal-truncated synthetic L1gamma (sL1gamma; 11-mer) is less active in inhibiting platelet aggregation than the native peptide. Results from Ala scan studies of the sL1gamma peptide indicated that replacement of the residues (P3, G7, P8, P9 or N10) resulted in a remarkable drop in the activity, whereas replacement of residues K2, P4 or K6 by Ala resulted in enhancement of the antiplatelet activity by at least 10-fold. To examine the activity of multimeric L1gamma, several multimeric peptides were synthesized using the multiple-antigen peptide system assembled on a branched lysine core and their antiplatelet activity was evaluated in vitro. The largest multimeric peptides showed a 1,000-fold increase in antiplatelet activity.