Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism

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Shafaee Abbas; PIRAYESH ISLAMIAN JALIL; Zarei Davoud; MOHAMMADI MOHSEN; NEJATI KOSHKI KAZEM; FARAJOLLAHI ALIREZA; AGHAMIRI SEYED MAHMOUD REZA; RAHMATI YAMCHI MOHAMMAD; BARADARAN BEHZAD; ASGHARI JAFARABADI MOHAMMAD

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Journal: Iranian Journal of Medical Sciences Year:2019 | Volume:44 | Issue:2 Page(s): 99-107

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Title

Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism

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Keywords

Deoxy

Glucose.Esophageal carcinoma.Metformin.Apoptosis

Abstract

Background: Both mitochondrial dysfunction and aerobic glycolysis are signs of growing aggressive cancer. If altered metabolism of cancer cell is intended, using the glycolysis inhibitor (2-Deoxyglucose (2DG)) would be a viable therapeutic method. The AMP-activated protein kinase (AMPK), as a metabolic sensor, could be activated with metformin and it can also launch a p53-dependent metabolic checkpoint and might inhibit cancer cell growth. Methods: After treatment with 5 mM metformin and/or 500 μ M 2DG, the TE1, TE8, and TE11 cellular viability and apoptosis were assessed by MTT, TUNEL, and ELISA methods. The changes in p53 and Bcl-2 genes expression levels were examined using real-time PCR method. Data were analyzed by Kruskal-Wallis test using the SPSS 17. 0 software. Results: Metformin and 2DG, alone and in combination, induced apoptosis in the cell lines. Real-time PCR revealed that metformin induced apoptosis in TE8 and TE11 cells by activating p53, down-regulating Bcl-2 expression. The induced apoptosis by 2DG raised by metformin and the combination modulated the expression of Bcl-2 protein in all cell lines and it was more effective in TE11 cell line. Conclusion: Metformin induced apoptosis in ESCC by down-regulating Bcl-2 expression, and up-regulating p53 and induced apoptosis increased by 2-Deoxy-d-glucose. Thus, the combination therapy is an effective therapeutic strategy for esophageal squamous cell carcinoma.

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APA: Copy

Shafaee, Abbas, PIRAYESH ISLAMIAN, JALIL, Zarei, Davoud, MOHAMMADI, MOHSEN, NEJATI KOSHKI, KAZEM, FARAJOLLAHI, ALIREZA, AGHAMIRI, SEYED MAHMOUD REZA, RAHMATI YAMCHI, MOHAMMAD, BARADARAN, BEHZAD, & ASGHARI JAFARABADI, MOHAMMAD. (2019). Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism. IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS), 44(2), 99-107. SID. https://sid.ir/paper/752523/en

Vancouver: Copy

Shafaee Abbas, PIRAYESH ISLAMIAN JALIL, Zarei Davoud, MOHAMMADI MOHSEN, NEJATI KOSHKI KAZEM, FARAJOLLAHI ALIREZA, AGHAMIRI SEYED MAHMOUD REZA, RAHMATI YAMCHI MOHAMMAD, BARADARAN BEHZAD, ASGHARI JAFARABADI MOHAMMAD. Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism. IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS)[Internet]. 2019;44(2):99-107. Available from: https://sid.ir/paper/752523/en

IEEE: Copy

Abbas Shafaee, JALIL PIRAYESH ISLAMIAN, Davoud Zarei, MOHSEN MOHAMMADI, KAZEM NEJATI KOSHKI, ALIREZA FARAJOLLAHI, SEYED MAHMOUD REZA AGHAMIRI, MOHAMMAD RAHMATI YAMCHI, BEHZAD BARADARAN, and MOHAMMAD ASGHARI JAFARABADI, “Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism,” IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS), vol. 44, no. 2, pp. 99–107, 2019, [Online]. Available: https://sid.ir/paper/752523/en

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