Metabolic modulation of Ewing sarcoma cells inhibits tumor growth and stem cell properties
| Autor: | Nino Rainusso, Jason T. Yustein, Ronald J. Bernardi, Ryan Shuck, Lyazat Kurenbekova, Atreyi Dasgupta, Matteo Trucco, David M. Loeb |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
cancer stem cells medicine.medical_specialty Programmed cell death 03 medical and health sciences 0302 clinical medicine Cancer stem cell Internal medicine Medicine Hematology business.industry Cancer 2DG medicine.disease 3. Good health 030104 developmental biology Oncology Apoptosis Cell culture 030220 oncology & carcinogenesis Immunology Cancer research Sarcoma Stem cell business metformin metabolism Ewing sarcoma Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Atreyi Dasgupta 1 , Matteo Trucco 2 , Nino Rainusso 1 , Ronald J. Bernardi 1 , Ryan Shuck 1 , Lyazat Kurenbekova 1 , David M. Loeb 3 and Jason T. Yustein 1, 4, 5 1 The Faris D. Virani Ewing Sarcoma Center at The Texas Children’s Cancer and Hematology Centers, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA 2 Sylvester Comprehensive Cancer Center, Department of Pediatrics, Hematology-Oncology, University of Miami-Miller School of Medicine, Miami, FL 33136, USA 3 Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, Baltimore, MD 21231, USA 4 Integrative Molecular and Biological Sciences Program, Baylor College of Medicine, Houston, TX 77030, USA 5 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA Correspondence to: Jason T. Yustein, email: yustein@bcm.edu Keywords: metabolism, cancer stem cells, Ewing sarcoma, 2DG, metformin Received: March 21, 2017 Accepted: July 20, 2017 Published: August 24, 2017 ABSTRACT Ewing sarcoma (EWS) is a highly aggressive and metabolically active malignant tumor. Metabolic activity can broadly be characterized by features of glycolytic activity and oxidative phosphorylation. We have further characterized metabolic features of EWS cells to identify potential therapeutic targets. EWS cells had significantly more glycolytic activity compared to their non-malignant counterparts. Thus, metabolic inhibitors of glycolysis such as 2-deoxy-D-glucose (2DG) and of the mitochondrial respiratory pathway, such as metformin, were evaluated as potential therapeutic agents against a panel of EWS cell lines in vitro . Results indicate that 2DG alone or in combination with metformin was effective at inducing cell death in EWS cell lines. The predominant mechanism of cell death appears to be through stimulating apoptosis leading into necrosis with concomitant activation of AMPK-α. Furthermore, we demonstrate that the use of metabolic modulators can target putative EWS stem cells, both in vitro and in vivo , and potentially overcome chemotherapeutic resistance in EWS. Based on these data, clinical strategies using drugs targeting tumor cell metabolism present a viable therapeutic modality against EWS. |
| Databáze: | OpenAIRE |
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