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 foc...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Royan Institute (ACECR), Tehran
2020-10-01
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| Series: | Cell Journal |
| Subjects: | |
| Online Access: | https://celljournal.org/journal/article/abstract/6798 |
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| author | Narges Rezaei Ali Neshasteh-Riz Zohreh Mazaheri Fereshteh Koosha Mahmood Hoormand |
| author_facet | Narges Rezaei Ali Neshasteh-Riz Zohreh Mazaheri Fereshteh Koosha Mahmood Hoormand |
| author_sort | Narges Rezaei |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T15:13:07Z |
| format | Article |
| id | doaj.art-2d3dcaca636040a1b7f287d23d94e1f5 |
| institution | Directory Open Access Journal |
| issn | 2228-5806 2228-5814 |
| language | English |
| last_indexed | 2024-12-22T15:13:07Z |
| publishDate | 2020-10-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | Cell Journal |
| spelling | doaj.art-2d3dcaca636040a1b7f287d23d94e1f52022-12-21T18:21:49ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142020-10-0122326327210.22074/cellj.2020.6798The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma CellsNarges Rezaei0Ali Neshasteh-Riz1Zohreh Mazaheri2Fereshteh Koosha3Mahmood Hoormand4Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, IranRadiation Biology Research Center, Iran University of Medical Sciences, Tehran, IranDepartment of Anatomical Sciences, Medical Sciences Faculty, Tarbiat Modares University, Tehran, IranRadiation Biology Research Center, Iran University of Medical Sciences, Tehran, IranDepartment of Pharmacology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, IranObjective: 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.https://celljournal.org/journal/article/abstract/6798apoptosisdisulfiramglioblastomairradiationmetformin |
| spellingShingle | Narges Rezaei Ali Neshasteh-Riz Zohreh Mazaheri Fereshteh Koosha Mahmood Hoormand The Combination of Metformin and Disulfiram-Cu for Effective Radiosensitization on Glioblastoma Cells Cell Journal apoptosis disulfiram glioblastoma irradiation metformin |
| 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 | apoptosis disulfiram glioblastoma irradiation metformin |
| url | https://celljournal.org/journal/article/abstract/6798 |
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