Metabolic Switch and Cytotoxic Effect of Metformin on Burkitt Lymphoma
Altered cellular energetic metabolism has recently emerged as important feature of neoplastic cells. Indeed, interfering with cancer cell metabolism might represent a suitable therapeutic strategy. In this study, we aimed to assess glucose metabolism activation in human lymphomas and evaluate how me...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.661102/full |
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| author | Irene Bagaloni Axel Visani Sara Biagiotti Annamaria Ruzzo Mohsen Navari Mohsen Navari Mohsen Navari Maryam Etebari Maryam Etebari Lucia Mundo Lucia Mundo Massimo Granai Massimo Granai Stefano Lazzi Alessandro Isidori Federica Loscocco Jiejin Li Lorenzo Leoncini Giuseppe Visani Mauro Magnani Pier Paolo Piccaluga Pier Paolo Piccaluga Pier Paolo Piccaluga Pier Paolo Piccaluga |
| author_facet | Irene Bagaloni Axel Visani Sara Biagiotti Annamaria Ruzzo Mohsen Navari Mohsen Navari Mohsen Navari Maryam Etebari Maryam Etebari Lucia Mundo Lucia Mundo Massimo Granai Massimo Granai Stefano Lazzi Alessandro Isidori Federica Loscocco Jiejin Li Lorenzo Leoncini Giuseppe Visani Mauro Magnani Pier Paolo Piccaluga Pier Paolo Piccaluga Pier Paolo Piccaluga Pier Paolo Piccaluga |
| author_sort | Irene Bagaloni |
| collection | DOAJ |
| description | Altered cellular energetic metabolism has recently emerged as important feature of neoplastic cells. Indeed, interfering with cancer cell metabolism might represent a suitable therapeutic strategy. In this study, we aimed to assess glucose metabolism activation in human lymphomas and evaluate how metformin can exert its action on lymphoma cells. We studied a large series of human lymphomas (N = 252) and an in vitro model of Burkitt lymphoma (BL) cells. We combined molecular biology techniques, including global gene expression profiling (GEP) analysis, quantitative PCR (qPCR) and Western blotting, and biochemical assays, aimed to assess pentose phosphate pathway, tricarboxylic acid (TCA) cycle, and aerobic glycolysis rates. We found that glucose metabolism is overall enhanced in most lymphoma subtypes, based on gene expression profiling (GEP), with general shift to aerobic glycolysis. By contrast, normal B cells only showed an overall increase in glucose usage during germinal center transition. Interestingly, not only highly proliferating aggressive lymphomas but also indolent ones, like marginal zone lymphomas, showed the phenomenon. Consistently, genes involved in glycolysis were confirmed to be overexpressed in BL cells by qPCR. Biochemical assays showed that while aerobic glycolysis is increased, TCA cycle is reduced. Finally, we showed that metformin can induce cell death in BL cells by stressing cellular metabolism through the induction of GLUT1, PKM2, and LDHA. In conclusion, we unveiled glucose metabolism abnormalities in human lymphomas and characterized the mechanism of action of metformin in Burkitt lymphoma model. |
| first_indexed | 2024-12-17T09:09:20Z |
| format | Article |
| id | doaj.art-305e9d07524b48dba08c61891a543639 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T09:09:20Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-305e9d07524b48dba08c61891a5436392022-12-21T21:55:18ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.661102661102Metabolic Switch and Cytotoxic Effect of Metformin on Burkitt LymphomaIrene Bagaloni0Axel Visani1Sara Biagiotti2Annamaria Ruzzo3Mohsen Navari4Mohsen Navari5Mohsen Navari6Maryam Etebari7Maryam Etebari8Lucia Mundo9Lucia Mundo10Massimo Granai11Massimo Granai12Stefano Lazzi13Alessandro Isidori14Federica Loscocco15Jiejin Li16Lorenzo Leoncini17Giuseppe Visani18Mauro Magnani19Pier Paolo Piccaluga20Pier Paolo Piccaluga21Pier Paolo Piccaluga22Pier Paolo Piccaluga23Department of Biomolecular Sciences (DISB), University of Urbino, Urbino, ItalyDepartment of Experimental, Diagnostic, and Specialty Medicine, Bologna University School of Medicine, Bologna, ItalyDepartment of Biomolecular Sciences (DISB), University of Urbino, Urbino, ItalyDepartment of Biomolecular Sciences (DISB), University of Urbino, Urbino, ItalyDepartment of Medical Biotechnology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, IranResearch Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, IranBioinformatics Research Group, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Experimental, Diagnostic, and Specialty Medicine, Bologna University School of Medicine, Bologna, ItalyDepartment of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, IranSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, ItalyHealth Research Institute, University of Limerick, Limerick, IrelandSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, ItalyDepartment of Pathology, Tubingen University, Tubingen, GermanySection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy0Hematology and Transplant Center, AORMN Marche Nord, Pesaro, Italy0Hematology and Transplant Center, AORMN Marche Nord, Pesaro, Italy1School of Biological and Chemical Sciences, Queen Mary University of London, London, United KingdomSection of Pathology, Department of Medical Biotechnology, University of Siena, Siena, Italy0Hematology and Transplant Center, AORMN Marche Nord, Pesaro, ItalyDepartment of Biomolecular Sciences (DISB), University of Urbino, Urbino, ItalyDepartment of Experimental, Diagnostic, and Specialty Medicine, Bologna University School of Medicine, Bologna, Italy1School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom2Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy3School of Health, Department of Pathology, Jomo Kenyatta University of Agriculture and Technology, Nairobi, KenyaAltered cellular energetic metabolism has recently emerged as important feature of neoplastic cells. Indeed, interfering with cancer cell metabolism might represent a suitable therapeutic strategy. In this study, we aimed to assess glucose metabolism activation in human lymphomas and evaluate how metformin can exert its action on lymphoma cells. We studied a large series of human lymphomas (N = 252) and an in vitro model of Burkitt lymphoma (BL) cells. We combined molecular biology techniques, including global gene expression profiling (GEP) analysis, quantitative PCR (qPCR) and Western blotting, and biochemical assays, aimed to assess pentose phosphate pathway, tricarboxylic acid (TCA) cycle, and aerobic glycolysis rates. We found that glucose metabolism is overall enhanced in most lymphoma subtypes, based on gene expression profiling (GEP), with general shift to aerobic glycolysis. By contrast, normal B cells only showed an overall increase in glucose usage during germinal center transition. Interestingly, not only highly proliferating aggressive lymphomas but also indolent ones, like marginal zone lymphomas, showed the phenomenon. Consistently, genes involved in glycolysis were confirmed to be overexpressed in BL cells by qPCR. Biochemical assays showed that while aerobic glycolysis is increased, TCA cycle is reduced. Finally, we showed that metformin can induce cell death in BL cells by stressing cellular metabolism through the induction of GLUT1, PKM2, and LDHA. In conclusion, we unveiled glucose metabolism abnormalities in human lymphomas and characterized the mechanism of action of metformin in Burkitt lymphoma model.https://www.frontiersin.org/articles/10.3389/fonc.2021.661102/fullglucose metabolismglycolysismetforminanaerobic glycolysisBurkitt lymphoma |
| spellingShingle | Irene Bagaloni Axel Visani Sara Biagiotti Annamaria Ruzzo Mohsen Navari Mohsen Navari Mohsen Navari Maryam Etebari Maryam Etebari Lucia Mundo Lucia Mundo Massimo Granai Massimo Granai Stefano Lazzi Alessandro Isidori Federica Loscocco Jiejin Li Lorenzo Leoncini Giuseppe Visani Mauro Magnani Pier Paolo Piccaluga Pier Paolo Piccaluga Pier Paolo Piccaluga Pier Paolo Piccaluga Metabolic Switch and Cytotoxic Effect of Metformin on Burkitt Lymphoma Frontiers in Oncology glucose metabolism glycolysis metformin anaerobic glycolysis Burkitt lymphoma |
| title | Metabolic Switch and Cytotoxic Effect of Metformin on Burkitt Lymphoma |
| title_full | Metabolic Switch and Cytotoxic Effect of Metformin on Burkitt Lymphoma |
| title_fullStr | Metabolic Switch and Cytotoxic Effect of Metformin on Burkitt Lymphoma |
| title_full_unstemmed | Metabolic Switch and Cytotoxic Effect of Metformin on Burkitt Lymphoma |
| title_short | Metabolic Switch and Cytotoxic Effect of Metformin on Burkitt Lymphoma |
| title_sort | metabolic switch and cytotoxic effect of metformin on burkitt lymphoma |
| topic | glucose metabolism glycolysis metformin anaerobic glycolysis Burkitt lymphoma |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.661102/full |
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