Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism
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 metabo...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Shiraz University of Medical Sciences
2019-03-01
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| Series: | Iranian Journal of Medical Sciences |
| Subjects: | |
| Online Access: | http://ijms.sums.ac.ir/article_44522_7ab70849b19909ee8dd86b721e96daba.pdf |
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| author | Abbas Shafaee Jalil Pirayesh Islamian Davoud Zarei Mohsen Mohammadi Kazem Nejati-Koshki Alireza Farajollahi Seyed Mahmoud Reza Aghamiri Mohammad Rahmati Yamchi Behzad Baradaran Mohammad Asghari Jafarabadi |
| author_facet | Abbas Shafaee Jalil Pirayesh Islamian Davoud Zarei Mohsen Mohammadi Kazem Nejati-Koshki Alireza Farajollahi Seyed Mahmoud Reza Aghamiri Mohammad Rahmati Yamchi Behzad Baradaran Mohammad Asghari Jafarabadi |
| author_sort | Abbas Shafaee |
| collection | DOAJ |
| description | 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 µM 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. |
| first_indexed | 2024-12-10T22:08:29Z |
| format | Article |
| id | doaj.art-2c8da5ce2aa94545b10a43f65a5390f7 |
| institution | Directory Open Access Journal |
| issn | 0253-0716 1735-3688 |
| language | English |
| last_indexed | 2024-12-10T22:08:29Z |
| publishDate | 2019-03-01 |
| publisher | Shiraz University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Medical Sciences |
| spelling | doaj.art-2c8da5ce2aa94545b10a43f65a5390f72022-12-22T01:31:40ZengShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-07161735-36882019-03-014429910710.30476/ijms.2019.4452244522Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell MetabolismAbbas Shafaee0Jalil Pirayesh Islamian1Davoud Zarei2Mohsen Mohammadi3Kazem Nejati-Koshki4Alireza Farajollahi5Seyed Mahmoud Reza Aghamiri6Mohammad Rahmati Yamchi7Behzad Baradaran8Mohammad Asghari Jafarabadi9Department of Radiology-Faculty of Paramedicine- Tabriz University of Medical Sciences, Tabriz, IranDepartment of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Medical Radiation Science, School of Paramedicine, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Medical Radiation Science, School of Paramedicine, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Medical Biotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, IranDepartment of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Radiation Medicine, Faculty of Nuclear Engineering, Shahid Beheshti University of Medical Sciences, Tehran, IranDepartment of Medical Biotechnology, Faculty of Advanced Medical Sciences, School of Medicine, Tabriz University of Medical Sciences, Tabriz, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Statistics and Epidemiology, Tabriz University of Medical Sciences, Tabriz, IranBackground: 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 µM 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.http://ijms.sums.ac.ir/article_44522_7ab70849b19909ee8dd86b721e96daba.pdf2-Deoxy-D-GlucoseEsophageal carcinomaMetforminapoptosis |
| spellingShingle | Abbas Shafaee Jalil Pirayesh Islamian Davoud Zarei Mohsen Mohammadi Kazem Nejati-Koshki Alireza Farajollahi Seyed Mahmoud Reza Aghamiri Mohammad Rahmati Yamchi Behzad Baradaran 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 2-Deoxy-D-Glucose Esophageal carcinoma Metformin apoptosis |
| title | Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism |
| title_full | Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism |
| title_fullStr | Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism |
| title_full_unstemmed | Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism |
| title_short | Induction of Apoptosis by a Combination of 2-Deoxyglucose and Metformin in Esophageal Squamous Cell Carcinoma by Targeting Cancer Cell Metabolism |
| title_sort | induction of apoptosis by a combination of 2 deoxyglucose and metformin in esophageal squamous cell carcinoma by targeting cancer cell metabolism |
| topic | 2-Deoxy-D-Glucose Esophageal carcinoma Metformin apoptosis |
| url | http://ijms.sums.ac.ir/article_44522_7ab70849b19909ee8dd86b721e96daba.pdf |
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