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Salinomycin Potentiates the Cytotoxic Effects of TRAIL on Glioblastoma Cell Lines

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to exhibit therapeutic activity in cancer. However, many tumors remain resistant to treatment with TRAIL. Therefore, small molecules that potentiate the cytotoxic effects of TRAIL could be used for combinatorial therap...

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Autores principales: Calzolari, Alessia, Saulle, Ernestina, De Angelis, Maria Laura, Pasquini, Luca, Boe, Alessandra, Pelacchi, Federica, Ricci-Vitiani, Lucia, Baiocchi, Marta, Testa, Ugo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989199/
https://www.ncbi.nlm.nih.gov/pubmed/24740347
http://dx.doi.org/10.1371/journal.pone.0094438
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author Calzolari, Alessia
Saulle, Ernestina
De Angelis, Maria Laura
Pasquini, Luca
Boe, Alessandra
Pelacchi, Federica
Ricci-Vitiani, Lucia
Baiocchi, Marta
Testa, Ugo
author_facet Calzolari, Alessia
Saulle, Ernestina
De Angelis, Maria Laura
Pasquini, Luca
Boe, Alessandra
Pelacchi, Federica
Ricci-Vitiani, Lucia
Baiocchi, Marta
Testa, Ugo
author_sort Calzolari, Alessia
collection PubMed
description Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to exhibit therapeutic activity in cancer. However, many tumors remain resistant to treatment with TRAIL. Therefore, small molecules that potentiate the cytotoxic effects of TRAIL could be used for combinatorial therapy. Here we found that the ionophore antibiotic salinomycin acts in synergism with TRAIL, enhancing TRAIL-induced apoptosis in glioma cells. Treatment with low doses of salinomycin in combination with TRAIL augmented the activation of caspase-3 and increased TRAIL-R2 cell surface expression. TRAIL-R2 upmodulation was required for mediating the stimulatory effect of salinomycin on TRAIL-mediated apoptosis, since it was abrogated by siRNA-mediated TRAIL-R2 knockdown. Salinomycin in synergism with TRAIL exerts a marked anti-tumor effect in nude mice xenografted with human glioblastoma cells. Our results suggest that the combination of TRAIL and salinomycin may be a useful tool to overcome TRAIL resistance in glioma cells and may represent a potential drug for treatment of these tumors. Importantly, salinomycin+TRAIL were able to induce cell death of well-defined glioblastoma stem-like lines.
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spelling pubmed-39891992014-04-21 Salinomycin Potentiates the Cytotoxic Effects of TRAIL on Glioblastoma Cell Lines Calzolari, Alessia Saulle, Ernestina De Angelis, Maria Laura Pasquini, Luca Boe, Alessandra Pelacchi, Federica Ricci-Vitiani, Lucia Baiocchi, Marta Testa, Ugo PLoS One Research Article Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to exhibit therapeutic activity in cancer. However, many tumors remain resistant to treatment with TRAIL. Therefore, small molecules that potentiate the cytotoxic effects of TRAIL could be used for combinatorial therapy. Here we found that the ionophore antibiotic salinomycin acts in synergism with TRAIL, enhancing TRAIL-induced apoptosis in glioma cells. Treatment with low doses of salinomycin in combination with TRAIL augmented the activation of caspase-3 and increased TRAIL-R2 cell surface expression. TRAIL-R2 upmodulation was required for mediating the stimulatory effect of salinomycin on TRAIL-mediated apoptosis, since it was abrogated by siRNA-mediated TRAIL-R2 knockdown. Salinomycin in synergism with TRAIL exerts a marked anti-tumor effect in nude mice xenografted with human glioblastoma cells. Our results suggest that the combination of TRAIL and salinomycin may be a useful tool to overcome TRAIL resistance in glioma cells and may represent a potential drug for treatment of these tumors. Importantly, salinomycin+TRAIL were able to induce cell death of well-defined glioblastoma stem-like lines. Public Library of Science 2014-04-16 /pmc/articles/PMC3989199/ /pubmed/24740347 http://dx.doi.org/10.1371/journal.pone.0094438 Text en © 2014 Calzolari et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Calzolari, Alessia
Saulle, Ernestina
De Angelis, Maria Laura
Pasquini, Luca
Boe, Alessandra
Pelacchi, Federica
Ricci-Vitiani, Lucia
Baiocchi, Marta
Testa, Ugo
Salinomycin Potentiates the Cytotoxic Effects of TRAIL on Glioblastoma Cell Lines
title Salinomycin Potentiates the Cytotoxic Effects of TRAIL on Glioblastoma Cell Lines
title_full Salinomycin Potentiates the Cytotoxic Effects of TRAIL on Glioblastoma Cell Lines
title_fullStr Salinomycin Potentiates the Cytotoxic Effects of TRAIL on Glioblastoma Cell Lines
title_full_unstemmed Salinomycin Potentiates the Cytotoxic Effects of TRAIL on Glioblastoma Cell Lines
title_short Salinomycin Potentiates the Cytotoxic Effects of TRAIL on Glioblastoma Cell Lines
title_sort salinomycin potentiates the cytotoxic effects of trail on glioblastoma cell lines
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3989199/
https://www.ncbi.nlm.nih.gov/pubmed/24740347
http://dx.doi.org/10.1371/journal.pone.0094438
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