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:	Alessia Calzolari, Ernestina Saulle, Maria Laura De Angelis, Luca Pasquini, Alessandra Boe, Federica Pelacchi, Lucia Ricci-Vitiani, Marta Baiocchi, Ugo Testa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/496bdd09b3f1404da9c6300769b67814
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spelling	oai:doaj.org-article:496bdd09b3f1404da9c6300769b678142021-11-18T08:22:50ZSalinomycin potentiates the cytotoxic effects of TRAIL on glioblastoma cell lines.1932-620310.1371/journal.pone.0094438https://doaj.org/article/496bdd09b3f1404da9c6300769b678142014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24740347/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Tumor 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.Alessia CalzolariErnestina SaulleMaria Laura De AngelisLuca PasquiniAlessandra BoeFederica PelacchiLucia Ricci-VitianiMarta BaiocchiUgo TestaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e94438 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alessia Calzolari Ernestina Saulle Maria Laura De Angelis Luca Pasquini Alessandra Boe Federica Pelacchi Lucia Ricci-Vitiani Marta Baiocchi Ugo Testa Salinomycin potentiates the cytotoxic effects of TRAIL on glioblastoma cell lines.
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.
format	article
author	Alessia Calzolari Ernestina Saulle Maria Laura De Angelis Luca Pasquini Alessandra Boe Federica Pelacchi Lucia Ricci-Vitiani Marta Baiocchi Ugo Testa
author_facet	Alessia Calzolari Ernestina Saulle Maria Laura De Angelis Luca Pasquini Alessandra Boe Federica Pelacchi Lucia Ricci-Vitiani Marta Baiocchi Ugo Testa
author_sort	Alessia Calzolari
title	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_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_sort	salinomycin potentiates the cytotoxic effects of trail on glioblastoma cell lines.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/496bdd09b3f1404da9c6300769b67814
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Salinomycin potentiates the cytotoxic effects of TRAIL on glioblastoma cell lines.

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