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Multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models
Reverting glycolytic metabolism is an attractive strategy for cancer therapy as upregulated glycolysis is a hallmark in various cancers. Dichloroacetate (DCA), long used to treat lactic acidosis in various pathologies, has emerged as a promising anti-cancer drug. By inhibiting the pyruvate dehydroge...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340254/ https://www.ncbi.nlm.nih.gov/pubmed/28082726 http://dx.doi.org/10.18632/oncotarget.13176 |
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author | Neveu, Marie-Aline Preter, Géraldine De Joudiou, Nicolas Bol, Anne Brender, Jeffery R. Saito, Keita Kishimoto, Shun Grégoire, Vincent Jordan, Bénédicte F. Krishna, Murali C. Feron, Olivier Gallez, Bernard |
author_facet | Neveu, Marie-Aline Preter, Géraldine De Joudiou, Nicolas Bol, Anne Brender, Jeffery R. Saito, Keita Kishimoto, Shun Grégoire, Vincent Jordan, Bénédicte F. Krishna, Murali C. Feron, Olivier Gallez, Bernard |
author_sort | Neveu, Marie-Aline |
collection | PubMed |
description | Reverting glycolytic metabolism is an attractive strategy for cancer therapy as upregulated glycolysis is a hallmark in various cancers. Dichloroacetate (DCA), long used to treat lactic acidosis in various pathologies, has emerged as a promising anti-cancer drug. By inhibiting the pyruvate dehydrogenase kinase, DCA reactivates the mitochondrial function and decreases the glycolytic flux in tumor cells resulting in cell cycle arrest and apoptosis. We recently documented that DCA was able to induce a metabolic switch preferentially in glycolytic cancer cells, leading to a more oxidative phenotype and decreasing proliferation, while oxidative cells remained less sensitive to DCA treatment. To evaluate the relevance of this observation in vivo, the aim of the present study was to characterize the effect of DCA in glycolytic MDA-MB-231 tumors and in oxidative SiHa tumors using advanced pharmacodynamic metabolic biomarkers. Oxygen consumption, studied by (17)O magnetic resonance spectroscopy, glucose uptake, evaluated by (18)F-FDG PET and pyruvate transformation into lactate, measured using hyperpolarized (13)C-magnetic resonance spectroscopy, were monitored before and 24 hours after DCA treatment in tumor bearing mice. In both tumor models, no clear metabolic shift was observed. Surprisingly, all these imaging parameters concur to the conclusion that both glycolytic tumors and oxidative tumors presented a similar response to DCA. These results highlight a major discordance in metabolic cancer cell bioenergetics between in vitro and in vivo setups, indicating critical role of the local microenvironment in tumor metabolic behaviors. |
format | Online Article Text |
id | pubmed-5340254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53402542017-03-08 Multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models Neveu, Marie-Aline Preter, Géraldine De Joudiou, Nicolas Bol, Anne Brender, Jeffery R. Saito, Keita Kishimoto, Shun Grégoire, Vincent Jordan, Bénédicte F. Krishna, Murali C. Feron, Olivier Gallez, Bernard Oncotarget Research Paper Reverting glycolytic metabolism is an attractive strategy for cancer therapy as upregulated glycolysis is a hallmark in various cancers. Dichloroacetate (DCA), long used to treat lactic acidosis in various pathologies, has emerged as a promising anti-cancer drug. By inhibiting the pyruvate dehydrogenase kinase, DCA reactivates the mitochondrial function and decreases the glycolytic flux in tumor cells resulting in cell cycle arrest and apoptosis. We recently documented that DCA was able to induce a metabolic switch preferentially in glycolytic cancer cells, leading to a more oxidative phenotype and decreasing proliferation, while oxidative cells remained less sensitive to DCA treatment. To evaluate the relevance of this observation in vivo, the aim of the present study was to characterize the effect of DCA in glycolytic MDA-MB-231 tumors and in oxidative SiHa tumors using advanced pharmacodynamic metabolic biomarkers. Oxygen consumption, studied by (17)O magnetic resonance spectroscopy, glucose uptake, evaluated by (18)F-FDG PET and pyruvate transformation into lactate, measured using hyperpolarized (13)C-magnetic resonance spectroscopy, were monitored before and 24 hours after DCA treatment in tumor bearing mice. In both tumor models, no clear metabolic shift was observed. Surprisingly, all these imaging parameters concur to the conclusion that both glycolytic tumors and oxidative tumors presented a similar response to DCA. These results highlight a major discordance in metabolic cancer cell bioenergetics between in vitro and in vivo setups, indicating critical role of the local microenvironment in tumor metabolic behaviors. Impact Journals LLC 2016-11-07 /pmc/articles/PMC5340254/ /pubmed/28082726 http://dx.doi.org/10.18632/oncotarget.13176 Text en Copyright: © 2016 Neveu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Neveu, Marie-Aline Preter, Géraldine De Joudiou, Nicolas Bol, Anne Brender, Jeffery R. Saito, Keita Kishimoto, Shun Grégoire, Vincent Jordan, Bénédicte F. Krishna, Murali C. Feron, Olivier Gallez, Bernard Multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models |
title | Multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models |
title_full | Multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models |
title_fullStr | Multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models |
title_full_unstemmed | Multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models |
title_short | Multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models |
title_sort | multi-modality imaging to assess metabolic response to dichloroacetate treatment in tumor models |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340254/ https://www.ncbi.nlm.nih.gov/pubmed/28082726 http://dx.doi.org/10.18632/oncotarget.13176 |
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