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

(Pages: 263-272)
Narges Rezaei, M.Sc, 1,2Ali Neshasteh-Riz, Ph.D, 1,2,*Zohreh Mazaheri, Ph.D, 3Fereshteh Koosha, Ph.D, 1,4Mahmood Hoormand, M.D., 5
Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
Department of Radiation Sciences, School of Paramedicine, Iran University of Medical Sciences, Tehran, Iran
Department of Anatomical Sciences, Medical Sciences Faculty, Tarbiat Modares University, Tehran, Iran
Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmacology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
Department of Radiation Sciences, School of Paramedicine, Iran University of Medical Sciences, Tehran, Iran
Department of Anatomical Sciences, Medical Sciences Faculty, Tarbiat Modares University, Tehran, Iran
Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmacology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
*Corresponding Address: P.O.Box: 1449614535 Department of Radiation Sciences School of Paramedicine Iran University of Medical Sciences Tehran Iran Email:neshastehriz@yahoo.com
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Rezaei N, Neshasteh-Riz A, Mazaheri Z, Koosha F, Hoormand M. The combination of metformin and disulfiram-cu for effective radiosensitization on glioblastoma cells. Cell J. 2020; 22(3): 263-272. doi: 10.22074/cellj.2020.6798.

Abstract

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.