Lebectin, a novel C-type lectin from Macrovipera lebetina venom, inhibits integrin-mediated adhesion, migration and invasion of human tumour cells

Abstract

The adhesion receptors of the integrin family play an essential role during tumour progression and thus represent interesting potential targets for the development of new therapeutic agents. The snake venom contains natural inhibitors of integrin-ligand interactions called disintegrins. It also contains C-type lectin proteins mainly known as modulators of platelet aggregation. In this study, we demonstrate that lebectin, a novel C-type lectin isolated from Macrovipera lebetina venom, displayed an anti-integrin activity. Lebectin inhibited the integrin-mediated attachment of various tumour cell lines to different adhesion substrata. The C-type lectin also completely blocked cell migration towards fibronectin in haptotaxis assays and prevented invasion of fibrin gels by tumour cells. In addition, lebectin proved to be a potent inhibitor of tumour cell proliferation. Although the specific integrins affected by lebectin are not identified in this study, the integrin alpha 5 beta 1 might be involved.

In Vitro Cytotoxic and Proapoptotic Activities of Anatolian Macrovipera Lebetina Obtusa (Dwigubski, 1832) Crude Venom on Cultured K562 Human Chronic Myelogenous Leukemia Cells.

“…8 Proteins with in vitro and in vivo anticancer activities, including metalloproteinase, disintegrin, PLA 2 , LAAO and CLP have been purified and identified in the venom of different subspecies of M. lebetina. 13,16,19,[36][37][38] These proteins exhibited their cytotoxic effects through different mechanisms such as integrin-blocking and apoptosis induction, resulting in the antiproliferative, antiadhesive and antiangiogenic activities.…”

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

“…19,20 Fraction IV, containing the anti-platelet aggregation activity with low molecular mass, was collected and lyophilized for further purification. It was applied to a reverse phase C8 column (250 Â 4.6 mm, 5 mm; Beckman; Fullerton, CA, USA) equilibrated with 0.1% trifluoroacetic acid (TFA) in 10% acetonitrile and then eluted at a flow rate of 0.8 ml/min with an acetonitrile linear gradient 10-63% over 45 min.…”

“…19,20 The fraction IV was the lowest concentration and exhibited antiplatelet aggregation activity and contained peptides with low molecular weight. 27 This fraction was collected, lyophilized and applied to a reversephase HPLC C8 column.…”

Lebectin and lebecetin, two C-type lectins from snake venom, inhibit α5β1 and αv-containing integrins

“…Lebectin is composed of two 16 kDa subunits linked by disulphide bonds. It displays an inhibitory activity on various integrin-mediated functions in tumour cells, including adhesion, proliferation and cell migration (Sarray et al, 2004). Lebecetin is a 30 kDa heterodimeric CLP that binds to GPIb and displays a potent anti-platelet activity (Sarray et al, 2003).…”