Publication: Lebein, a snake venom disintegrin, induces apoptosis in human melanoma cells
Authors
Hammouda, Manel B. ; Zakraoui, Ons ; Aloui, Zohra ; Riahi-Chebbi, Ichrak ; Karoui, Habib ; Essafi Benkhadir, Khadija ; Montenegro Arce, María Fernanda ; Rodríguez López, José Neptuno ; Sánchez del Campo Ferrer, Luis
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Publisher
MDPI
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DOI
https://doi.org/10.3390/toxins8070206
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info:eu-repo/semantics/article
Description
© 2016 by the authors. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/
This document is the Published version of a Published Work that appeared in final form in Toxins. To access the final edited and published work see https://doi.org/10.3390/toxins8070206
Abstract
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.
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Citation
Toxins, 2016, Vol. 8, N. 7: 206
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by/4.0/