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Anti-Tumor Effects of Bak-Proteoliposomes against Glioblastoma

Despite palliative treatments, glioblastoma (GBM) remains a devastating malignancy with a mean survival of about 15 months after diagnosis. Programmed cell-death is de-regulated in almost all GBM and the re-activation of the mitochondrial apoptotic pathway through exogenous bioactive proteins may re...

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Autores principales: Liguori, Lavinia, Pastorino, Fabio, Rousset, Xavier, Alfano, Silvia, Cortes, Sandra, Emionite, Laura, Daga, Antonio, Ponzoni, Mirco, Lenormand, Jean-Luc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332045/
https://www.ncbi.nlm.nih.gov/pubmed/26340616
http://dx.doi.org/10.3390/molecules200915893
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author Liguori, Lavinia
Pastorino, Fabio
Rousset, Xavier
Alfano, Silvia
Cortes, Sandra
Emionite, Laura
Daga, Antonio
Ponzoni, Mirco
Lenormand, Jean-Luc
author_facet Liguori, Lavinia
Pastorino, Fabio
Rousset, Xavier
Alfano, Silvia
Cortes, Sandra
Emionite, Laura
Daga, Antonio
Ponzoni, Mirco
Lenormand, Jean-Luc
author_sort Liguori, Lavinia
collection PubMed
description Despite palliative treatments, glioblastoma (GBM) remains a devastating malignancy with a mean survival of about 15 months after diagnosis. Programmed cell-death is de-regulated in almost all GBM and the re-activation of the mitochondrial apoptotic pathway through exogenous bioactive proteins may represent a powerful therapeutic tool to treat multidrug resistant GBM. We have reported that human Bak protein integrated in Liposomes (LB) was able, in vitro, to activate the mitochondrial apoptotic pathway in colon cancer cells. To evaluate the anti-tumor effects of LB on GBM, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and Western blot analysis were performed on GL26 murine cell line. LB treatment shows a dose-dependent inhibition of cell viability, followed by an up-regulation of Bax and a down-modulation of JNK1 proteins. In GL26-bearing mice, two different routes of administration were tested: intra-tumor and intravenous. Biodistribution, tumor growth and animal survival rates were followed. LB show long-lasting tumor accumulation. Moreover, the intra-tumor administration of LB induces tumor growth delay and total tumor regression in about 40% of treated mice, while the intravenous injection leads to a significant increased life span of mice paralleled by an increased tumor cells apoptosis. Our findings are functional to the design of LB with potentiated therapeutic efficacy for GBM.
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spelling pubmed-63320452019-01-24 Anti-Tumor Effects of Bak-Proteoliposomes against Glioblastoma Liguori, Lavinia Pastorino, Fabio Rousset, Xavier Alfano, Silvia Cortes, Sandra Emionite, Laura Daga, Antonio Ponzoni, Mirco Lenormand, Jean-Luc Molecules Article Despite palliative treatments, glioblastoma (GBM) remains a devastating malignancy with a mean survival of about 15 months after diagnosis. Programmed cell-death is de-regulated in almost all GBM and the re-activation of the mitochondrial apoptotic pathway through exogenous bioactive proteins may represent a powerful therapeutic tool to treat multidrug resistant GBM. We have reported that human Bak protein integrated in Liposomes (LB) was able, in vitro, to activate the mitochondrial apoptotic pathway in colon cancer cells. To evaluate the anti-tumor effects of LB on GBM, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and Western blot analysis were performed on GL26 murine cell line. LB treatment shows a dose-dependent inhibition of cell viability, followed by an up-regulation of Bax and a down-modulation of JNK1 proteins. In GL26-bearing mice, two different routes of administration were tested: intra-tumor and intravenous. Biodistribution, tumor growth and animal survival rates were followed. LB show long-lasting tumor accumulation. Moreover, the intra-tumor administration of LB induces tumor growth delay and total tumor regression in about 40% of treated mice, while the intravenous injection leads to a significant increased life span of mice paralleled by an increased tumor cells apoptosis. Our findings are functional to the design of LB with potentiated therapeutic efficacy for GBM. MDPI 2015-09-01 /pmc/articles/PMC6332045/ /pubmed/26340616 http://dx.doi.org/10.3390/molecules200915893 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liguori, Lavinia
Pastorino, Fabio
Rousset, Xavier
Alfano, Silvia
Cortes, Sandra
Emionite, Laura
Daga, Antonio
Ponzoni, Mirco
Lenormand, Jean-Luc
Anti-Tumor Effects of Bak-Proteoliposomes against Glioblastoma
title Anti-Tumor Effects of Bak-Proteoliposomes against Glioblastoma
title_full Anti-Tumor Effects of Bak-Proteoliposomes against Glioblastoma
title_fullStr Anti-Tumor Effects of Bak-Proteoliposomes against Glioblastoma
title_full_unstemmed Anti-Tumor Effects of Bak-Proteoliposomes against Glioblastoma
title_short Anti-Tumor Effects of Bak-Proteoliposomes against Glioblastoma
title_sort anti-tumor effects of bak-proteoliposomes against glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332045/
https://www.ncbi.nlm.nih.gov/pubmed/26340616
http://dx.doi.org/10.3390/molecules200915893
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