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Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification

Extracellular acidification has been shown to be an important characteristic of invasive tumors, as it promotes invasion and migration but also resistance to treatments. Targeting transporters involved in the regulation of tumor pH constitutes a promising anti-tumor approach, as it would disrupt cel...

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Autores principales: Buyse, Chloe, Joudiou, Nicolas, Warscotte, Aude, Richiardone, Elena, Mignion, Lionel, Corbet, Cyril, Gallez, Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230831/
https://www.ncbi.nlm.nih.gov/pubmed/35736489
http://dx.doi.org/10.3390/metabo12060557
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author Buyse, Chloe
Joudiou, Nicolas
Warscotte, Aude
Richiardone, Elena
Mignion, Lionel
Corbet, Cyril
Gallez, Bernard
author_facet Buyse, Chloe
Joudiou, Nicolas
Warscotte, Aude
Richiardone, Elena
Mignion, Lionel
Corbet, Cyril
Gallez, Bernard
author_sort Buyse, Chloe
collection PubMed
description Extracellular acidification has been shown to be an important characteristic of invasive tumors, as it promotes invasion and migration but also resistance to treatments. Targeting transporters involved in the regulation of tumor pH constitutes a promising anti-tumor approach, as it would disrupt cellular pH homeostasis and negatively impact tumor growth. In this study, we evaluated the impact of syrosingopine, an inhibitor of MCT1 and MCT4, as a modulator of tumor metabolism and extracellular acidification in human breast cancer (MDA-MB-231) and pharyngeal squamous cell carcinoma (FaDu) cell models. In both models in vitro, we observed that exposure to syrosingopine led to a decrease in the extracellular acidification rate, intracellular pH, glucose consumption, lactate secretion and tumor cell proliferation with an increase in the number of late apoptotic/necrotic cells. However, in vivo experiments using the MDA-MB-231 model treated with a daily injection of syrosingopine did not reveal any significant change in extracellular pH (pHe) (as measured using CEST-MRI) or primary tumor growth. Overall, our study suggests that targeting MCT could lead to profound changes in tumor cell metabolism and proliferation, and it warrants further research to identify candidates without off-target effects.
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spelling pubmed-92308312022-06-25 Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification Buyse, Chloe Joudiou, Nicolas Warscotte, Aude Richiardone, Elena Mignion, Lionel Corbet, Cyril Gallez, Bernard Metabolites Article Extracellular acidification has been shown to be an important characteristic of invasive tumors, as it promotes invasion and migration but also resistance to treatments. Targeting transporters involved in the regulation of tumor pH constitutes a promising anti-tumor approach, as it would disrupt cellular pH homeostasis and negatively impact tumor growth. In this study, we evaluated the impact of syrosingopine, an inhibitor of MCT1 and MCT4, as a modulator of tumor metabolism and extracellular acidification in human breast cancer (MDA-MB-231) and pharyngeal squamous cell carcinoma (FaDu) cell models. In both models in vitro, we observed that exposure to syrosingopine led to a decrease in the extracellular acidification rate, intracellular pH, glucose consumption, lactate secretion and tumor cell proliferation with an increase in the number of late apoptotic/necrotic cells. However, in vivo experiments using the MDA-MB-231 model treated with a daily injection of syrosingopine did not reveal any significant change in extracellular pH (pHe) (as measured using CEST-MRI) or primary tumor growth. Overall, our study suggests that targeting MCT could lead to profound changes in tumor cell metabolism and proliferation, and it warrants further research to identify candidates without off-target effects. MDPI 2022-06-17 /pmc/articles/PMC9230831/ /pubmed/35736489 http://dx.doi.org/10.3390/metabo12060557 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Buyse, Chloe
Joudiou, Nicolas
Warscotte, Aude
Richiardone, Elena
Mignion, Lionel
Corbet, Cyril
Gallez, Bernard
Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification
title Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification
title_full Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification
title_fullStr Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification
title_full_unstemmed Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification
title_short Evaluation of Syrosingopine, an MCT Inhibitor, as Potential Modulator of Tumor Metabolism and Extracellular Acidification
title_sort evaluation of syrosingopine, an mct inhibitor, as potential modulator of tumor metabolism and extracellular acidification
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230831/
https://www.ncbi.nlm.nih.gov/pubmed/35736489
http://dx.doi.org/10.3390/metabo12060557
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