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The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma Cells

OBJECTIVE: Glioblastoma (GBM) is one of the devastating types of primary brain tumors with a negligible response to standard therapy. Repurposing drugs, such as disulfiram (DSF) and metformin (Met) have shown antitumor properties in different cell lines, including GBM. In the present study, we focus...

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Autores principales: Rezaei, Narges, Neshasteh-Riz, Ali, Mazaheri, Zohreh, Koosha, Fereshteh, Hoormand, Mahmood
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royan Institute 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947006/
https://www.ncbi.nlm.nih.gov/pubmed/31863651
http://dx.doi.org/10.22074/cellj.2020.6798
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author Rezaei, Narges
Neshasteh-Riz, Ali
Mazaheri, Zohreh
Koosha, Fereshteh
Hoormand, Mahmood
author_facet Rezaei, Narges
Neshasteh-Riz, Ali
Mazaheri, Zohreh
Koosha, Fereshteh
Hoormand, Mahmood
author_sort Rezaei, Narges
collection PubMed
description OBJECTIVE: Glioblastoma (GBM) is one of the devastating types of primary brain tumors with a negligible response to standard therapy. Repurposing drugs, such as disulfiram (DSF) and metformin (Met) have shown antitumor properties in different cell lines, including GBM. In the present study, we focused on the combinatory effect of Met and DSF-Cu on the induction of apoptosis in U87-MG cells exposed to 6-MV X-ray beams. MATERIALS AND METHODS: In this experimental study, the MTT assay was performed to evaluate the cytotoxicity of each drug, along with the combinatory use of both. After irradiation, the apoptotic cells were assessed using the flow cytometry, western blot, and real-time polymerase chain reaction (RT-PCR) to analyze the expression of some cell death markers such as BAX and BCL-2. RESULTS: The synergistic application of both Met and DSF had cytotoxic impacts on the U87-MG cell line and made them sensitized to irradiation. The combinatory usage of both drugs significantly decreased the cells growth, induced apoptosis, and caused the upregulation of BAX, P53, CASPASE-3, and it also markedly downregulated the expression of the anti-apoptotic protein BCL-2 at the gene and protein levels. CONCLUSION: It seems that the synergistic application of both Met and DSF with the support of irradiation can remarkably restrict the growth of the U87-MG cell line. This may trigger apoptosis via the stimulation of the intrinsic pathway. The combinatory use of Met and DSF in the presence of irradiation could be applied for patients afflicted with GBM.
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spelling pubmed-69470062020-10-01 The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma Cells Rezaei, Narges Neshasteh-Riz, Ali Mazaheri, Zohreh Koosha, Fereshteh Hoormand, Mahmood Cell J Original Article OBJECTIVE: Glioblastoma (GBM) is one of the devastating types of primary brain tumors with a negligible response to standard therapy. Repurposing drugs, such as disulfiram (DSF) and metformin (Met) have shown antitumor properties in different cell lines, including GBM. In the present study, we focused on the combinatory effect of Met and DSF-Cu on the induction of apoptosis in U87-MG cells exposed to 6-MV X-ray beams. MATERIALS AND METHODS: In this experimental study, the MTT assay was performed to evaluate the cytotoxicity of each drug, along with the combinatory use of both. After irradiation, the apoptotic cells were assessed using the flow cytometry, western blot, and real-time polymerase chain reaction (RT-PCR) to analyze the expression of some cell death markers such as BAX and BCL-2. RESULTS: The synergistic application of both Met and DSF had cytotoxic impacts on the U87-MG cell line and made them sensitized to irradiation. The combinatory usage of both drugs significantly decreased the cells growth, induced apoptosis, and caused the upregulation of BAX, P53, CASPASE-3, and it also markedly downregulated the expression of the anti-apoptotic protein BCL-2 at the gene and protein levels. CONCLUSION: It seems that the synergistic application of both Met and DSF with the support of irradiation can remarkably restrict the growth of the U87-MG cell line. This may trigger apoptosis via the stimulation of the intrinsic pathway. The combinatory use of Met and DSF in the presence of irradiation could be applied for patients afflicted with GBM. Royan Institute 2020 2019-12-15 /pmc/articles/PMC6947006/ /pubmed/31863651 http://dx.doi.org/10.22074/cellj.2020.6798 Text en The Cell Journal (Yakhteh) is an open access journal which means the articles are freely available online for any individual author to download and use the providing address. The journal is licensed under a Creative Commons Attribution-Non Commercial 3.0 Unported License which allows the author(s) to hold the copyright without restrictions that is permitting unrestricted use, distribution, and reproduction in any medium provided the original work is properly cited. http://creativecommons.org/licenses/by/3/ 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 work is properly cited.
spellingShingle Original Article
Rezaei, Narges
Neshasteh-Riz, Ali
Mazaheri, Zohreh
Koosha, Fereshteh
Hoormand, Mahmood
The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma Cells
title The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma Cells
title_full The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma Cells
title_fullStr The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma Cells
title_full_unstemmed The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma Cells
title_short The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma Cells
title_sort combination of metformin and disulfiram-cu for effective radiosensitization on glioblastoma cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947006/
https://www.ncbi.nlm.nih.gov/pubmed/31863651
http://dx.doi.org/10.22074/cellj.2020.6798
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