{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:05:58Z","timestamp":1793066758838,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2016,7,5]],"date-time":"2016-07-05T00:00:00Z","timestamp":1467676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/toxins8070206","type":"journal-article","created":{"date-parts":[[2016,7,5]],"date-time":"2016-07-05T10:06:19Z","timestamp":1467713179000},"page":"206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Lebein, a Snake Venom Disintegrin, Induces Apoptosis in Human Melanoma Cells"],"prefix":"10.3390","volume":"8","author":[{"given":"Manel","family":"Hammouda","sequence":"first","affiliation":[{"name":"Laboratoire d\u2019Epid\u00e9miologie Mol\u00e9culaire et Pathologie Exp\u00e9rimentale Appliqu\u00e9e Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, Tunisia"},{"name":"Universit\u00e9 de Tunis El Manar, 1068 Tunis, Tunisia"},{"name":"Department of Biochemistry and Molecular Biology A, School of Biology, University of Murcia, 30100 Espinardo, Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Montenegro","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology A, School of Biology, University of Murcia, 30100 Espinardo, Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"S\u00e1nchez-del-Campo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology A, School of Biology, University of Murcia, 30100 Espinardo, Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ons","family":"Zakraoui","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Epid\u00e9miologie Mol\u00e9culaire et Pathologie Exp\u00e9rimentale Appliqu\u00e9e Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, Tunisia"},{"name":"Universit\u00e9 de Tunis El Manar, 1068 Tunis, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohra","family":"Aloui","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Epid\u00e9miologie Mol\u00e9culaire et Pathologie Exp\u00e9rimentale Appliqu\u00e9e Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, Tunisia"},{"name":"Universit\u00e9 de Tunis El Manar, 1068 Tunis, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichrak","family":"Riahi-Chebbi","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Epid\u00e9miologie Mol\u00e9culaire et Pathologie Exp\u00e9rimentale Appliqu\u00e9e Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, Tunisia"},{"name":"Universit\u00e9 de Tunis El Manar, 1068 Tunis, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4363-6300","authenticated-orcid":false,"given":"Habib","family":"Karoui","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Epid\u00e9miologie Mol\u00e9culaire et Pathologie Exp\u00e9rimentale Appliqu\u00e9e Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, Tunisia"},{"name":"Universit\u00e9 de Tunis El Manar, 1068 Tunis, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Rodr\u00edguez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology A, School of Biology, University of Murcia, 30100 Espinardo, Murcia, Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biosanitaria (IMIB), 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1371-1963","authenticated-orcid":false,"given":"Khadija","family":"Essafi-Benkhadir","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Epid\u00e9miologie Mol\u00e9culaire et Pathologie Exp\u00e9rimentale Appliqu\u00e9e Aux Maladies Infectieuses (LR11IPT04), Institut Pasteur de Tunis, 1002 Tunis, Tunisia"},{"name":"Universit\u00e9 de Tunis El Manar, 1068 Tunis, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ascierto, P.A., Streicher, H.Z., and Sznol, M. 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