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

Abstract

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 a1b1 integrin. It was thus able to inhibit both adhesion and migration of PC12 and a1b1 integrin-expressing CHO cells (CHO-a1) 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. Laboratory Investigation (2005) 85, 1507-1516.

Leberagin-C, A disintegrin-like/cysteine-rich protein from Macrovipera lebetina transmediterranea venom, inhibits alphavbeta3 integrin-mediated cell adhesion

“…The short KTS-disintegrin (lebestatin) targeting alpha1beta1 integrin (Olfa et al, 2005) and two C-type lectin proteins (lebecetin and lebectin) that inhibit alpha5beta1 and alphav integrins (Sarray et al, 2007). We describe, herein, the isolation and characterization of leberagin-C, a D/C protein.…”

“…The crude venom of M. lebetina transmediterranea was separated by gel filtration on a Sephadex G-75 column as previously described (Sarray et al, 2004;Olfa et al, 2005). Six major fractions were collected and screened for their adhesive activity on IGR39 and HT29-D4 cancerous cells using different ECM components as matrix (data not shown).…”

“…Purified leberagin-C was reduced and alkylated as previously described (Olfa et al, 2005). The mixture was immediately desalted by reverse-phase HPLC on a C18 column as described above for protein purification.…”

MTA1 induced angiogenesis, migration and tumor growth is inhibited by Glycyrrhiza glabra

“…CAM assay was performed as described previously [25]. In brief, the fertilized eggs were incubated at 37 o C in a humidified and sterile atmosphere for 10 days.…”

Effect of VP12 and viperistatin on inhibition of collagen receptors: dependent melanoma metastasis

“…21 Disintegrins that antagonize the function of the α1β1 integrin are short monomeric disintegrins. Currently, only four α1β1 integrinblocking disintegrins, obtustatin, 22 viperistatin, 23 jerdostatin 24 and lebestatin, 25 have been reported. All of them contain a KTS motif in their active site, except jerdostain which displays RTS.…”