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Evaluation of the cytotoxic and immunogenic potential of temozolamide, panobinostat, and Lophophora williamsii extract against C6 glioma cells

Glioblastoma multiforme is a malignant neoplasm of the brain with poor prognosis. The first-line drug against glioblastoma is the alkylating agent temozolamide (TMZ); unfortunately, treatment resistance and tumor re-incidence are common. In some cases, immunogenic cell death (ICD) inducers can decre...

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Autores principales: Franco-Molina, Moisés Armides, Santana-Krímskaya, Silvia Elena, Madrigal-de-León, Luis Mario, Coronado-Cerda, Erika Evangelina, Zárate-Triviño, Diana Ginette, Hernández-Martínez, Sara Paola, García-Coronado, Paola Leonor, Rodríguez-Padilla, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Leibniz Research Centre for Working Environment and Human Factors 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056056/
https://www.ncbi.nlm.nih.gov/pubmed/33883986
http://dx.doi.org/10.17179/excli2020-3181
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author Franco-Molina, Moisés Armides
Santana-Krímskaya, Silvia Elena
Madrigal-de-León, Luis Mario
Coronado-Cerda, Erika Evangelina
Zárate-Triviño, Diana Ginette
Hernández-Martínez, Sara Paola
García-Coronado, Paola Leonor
Rodríguez-Padilla, Cristina
author_facet Franco-Molina, Moisés Armides
Santana-Krímskaya, Silvia Elena
Madrigal-de-León, Luis Mario
Coronado-Cerda, Erika Evangelina
Zárate-Triviño, Diana Ginette
Hernández-Martínez, Sara Paola
García-Coronado, Paola Leonor
Rodríguez-Padilla, Cristina
author_sort Franco-Molina, Moisés Armides
collection PubMed
description Glioblastoma multiforme is a malignant neoplasm of the brain with poor prognosis. The first-line drug against glioblastoma is the alkylating agent temozolamide (TMZ); unfortunately, treatment resistance and tumor re-incidence are common. In some cases, immunogenic cell death (ICD) inducers can decrease treatment resistance and tumor recurrence by stimulating an antitumor specific immune response. Not all ICD inducers, however, are suitable for glioma patients because of the low permeability of the blood-brain barrier (BBB). Panobinostat (PAN), a histone deacetylase inhibitor and Lophophora williamsii (LW) extract can pass through the BBB and have antitumor properties. The aim of this study is to evaluate the cytotoxic potential of TMZ, PAN and LW extract against the glioma C6 cell line, and its role in the release of damage-associated molecular patterns (DAMPs), which is a hallmark of ICD. Our results indicate that all treatments induce cellular death in a time- and concentration-dependent manner, and that PAN and LW extract induce apoptosis, whereas TMZ induces apoptosis and necrosis. Also, that some of the treatments and their sequential administration induce the release of DAMPs. Furthermore, in a rat glioma model, we observed that all treatments decreased tumor volume, but the in vivo cell death mechanism was not ICD. Our findings indicate that TMZ, PAN, and LW combination have a cytotoxic effect against glioma cells but do not induce ICD.
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spelling pubmed-80560562021-04-20 Evaluation of the cytotoxic and immunogenic potential of temozolamide, panobinostat, and Lophophora williamsii extract against C6 glioma cells Franco-Molina, Moisés Armides Santana-Krímskaya, Silvia Elena Madrigal-de-León, Luis Mario Coronado-Cerda, Erika Evangelina Zárate-Triviño, Diana Ginette Hernández-Martínez, Sara Paola García-Coronado, Paola Leonor Rodríguez-Padilla, Cristina EXCLI J Original Article Glioblastoma multiforme is a malignant neoplasm of the brain with poor prognosis. The first-line drug against glioblastoma is the alkylating agent temozolamide (TMZ); unfortunately, treatment resistance and tumor re-incidence are common. In some cases, immunogenic cell death (ICD) inducers can decrease treatment resistance and tumor recurrence by stimulating an antitumor specific immune response. Not all ICD inducers, however, are suitable for glioma patients because of the low permeability of the blood-brain barrier (BBB). Panobinostat (PAN), a histone deacetylase inhibitor and Lophophora williamsii (LW) extract can pass through the BBB and have antitumor properties. The aim of this study is to evaluate the cytotoxic potential of TMZ, PAN and LW extract against the glioma C6 cell line, and its role in the release of damage-associated molecular patterns (DAMPs), which is a hallmark of ICD. Our results indicate that all treatments induce cellular death in a time- and concentration-dependent manner, and that PAN and LW extract induce apoptosis, whereas TMZ induces apoptosis and necrosis. Also, that some of the treatments and their sequential administration induce the release of DAMPs. Furthermore, in a rat glioma model, we observed that all treatments decreased tumor volume, but the in vivo cell death mechanism was not ICD. Our findings indicate that TMZ, PAN, and LW combination have a cytotoxic effect against glioma cells but do not induce ICD. Leibniz Research Centre for Working Environment and Human Factors 2021-03-09 /pmc/articles/PMC8056056/ /pubmed/33883986 http://dx.doi.org/10.17179/excli2020-3181 Text en Copyright © 2021 Franco-Molina et al. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ) You are free to copy, distribute and transmit the work, provided the original author and source are credited.
spellingShingle Original Article
Franco-Molina, Moisés Armides
Santana-Krímskaya, Silvia Elena
Madrigal-de-León, Luis Mario
Coronado-Cerda, Erika Evangelina
Zárate-Triviño, Diana Ginette
Hernández-Martínez, Sara Paola
García-Coronado, Paola Leonor
Rodríguez-Padilla, Cristina
Evaluation of the cytotoxic and immunogenic potential of temozolamide, panobinostat, and Lophophora williamsii extract against C6 glioma cells
title Evaluation of the cytotoxic and immunogenic potential of temozolamide, panobinostat, and Lophophora williamsii extract against C6 glioma cells
title_full Evaluation of the cytotoxic and immunogenic potential of temozolamide, panobinostat, and Lophophora williamsii extract against C6 glioma cells
title_fullStr Evaluation of the cytotoxic and immunogenic potential of temozolamide, panobinostat, and Lophophora williamsii extract against C6 glioma cells
title_full_unstemmed Evaluation of the cytotoxic and immunogenic potential of temozolamide, panobinostat, and Lophophora williamsii extract against C6 glioma cells
title_short Evaluation of the cytotoxic and immunogenic potential of temozolamide, panobinostat, and Lophophora williamsii extract against C6 glioma cells
title_sort evaluation of the cytotoxic and immunogenic potential of temozolamide, panobinostat, and lophophora williamsii extract against c6 glioma cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056056/
https://www.ncbi.nlm.nih.gov/pubmed/33883986
http://dx.doi.org/10.17179/excli2020-3181
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