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Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells

Laboratoire d’Epidémiologie Moléculaire et Pathologie Expérimentale Appliquée Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, Tunisia
Université de Tunis El Manar, 1068 Tunis, Tunisia
Department of Biochemistry and Molecular Biology A, School of Biology, University of Murcia, 30100 Espinardo, Murcia, Spain
Instituto Murciano de Investigación Biosanitaria (IMIB), 30120 Murcia, Spain
Authors to whom correspondence should be addressed.
Academic Editor: Frank S. Markland
Toxins 2016, 8(7), 206;
Received: 4 May 2016 / Revised: 22 June 2016 / Accepted: 1 July 2016 / Published: 5 July 2016
(This article belongs to the Section Animal Venoms)
PDF [2401 KB, uploaded 5 July 2016]


Melanoma, the most threatening form of skin cancer, has a very poor prognosis and is characterized by its very invasive and chemoresistant properties. Despite the recent promising news from the field of immunotherapy, there is an urgent need for new therapeutic approaches that are free of resistance mechanisms and side effects. Anti-neoplasic properties have been highlighted for different disintegrins from snake venom including Lebein; however, the exact effect of Lebein on melanoma has not yet been defined. In this study, we showed that Lebein blocks melanoma cell proliferation and induces a more differentiated phenotype with inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and microphthalmia-associated transcription factor (MITF) overexpression. Melanoma cells became detached but were less invasive with upregulation of E-cadherin after Lebein exposure. Lebein induced a caspase-independent apoptotic program with apoptosis inducing factor (AIF), BCL-2-associated X protein (BAX) and Bim overexpression together with downregulation of B-cell lymphoma-2 (BCL-2). It generated a distinct response in reactive oxygen species (ROS) generation and p53 levels depending on the p53 cell line status (wild type or mutant). Therefore, we propose Lebein as a new candidate for development of potential therapies for melanoma. View Full-Text
Keywords: Lebein; disintegrin; snake venom; Macrovipera lebetina; melanoma; apoptosis Lebein; disintegrin; snake venom; Macrovipera lebetina; melanoma; apoptosis

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Hammouda, M.B.; Montenegro, M.F.; Sánchez-del-Campo, L.; Zakraoui, O.; Aloui, Z.; Riahi-Chebbi, I.; Karoui, H.; Rodríguez-López, J.N.; Essafi-Benkhadir, K. Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells. Toxins 2016, 8, 206.

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