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Glutamine Starvation Affects Cell Cycle, Oxidative Homeostasis and Metabolism in Colorectal Cancer Cells

Cancer cells adjust their metabolism to meet energy demands. In particular, glutamine addiction represents a distinctive feature of several types of tumors, including colorectal cancer. In this study, four colorectal cancer cell lines (Caco-2, HCT116, HT29 and SW480) were cultured with or without gl...

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Autores principales: Spada, Martina, Piras, Cristina, Diana, Giulia, Leoni, Vera Piera, Frau, Daniela Virginia, Serreli, Gabriele, Simbula, Gabriella, Loi, Roberto, Noto, Antonio, Murgia, Federica, Caria, Paola, Atzori, Luigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045305/
https://www.ncbi.nlm.nih.gov/pubmed/36978930
http://dx.doi.org/10.3390/antiox12030683
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author Spada, Martina
Piras, Cristina
Diana, Giulia
Leoni, Vera Piera
Frau, Daniela Virginia
Serreli, Gabriele
Simbula, Gabriella
Loi, Roberto
Noto, Antonio
Murgia, Federica
Caria, Paola
Atzori, Luigi
author_facet Spada, Martina
Piras, Cristina
Diana, Giulia
Leoni, Vera Piera
Frau, Daniela Virginia
Serreli, Gabriele
Simbula, Gabriella
Loi, Roberto
Noto, Antonio
Murgia, Federica
Caria, Paola
Atzori, Luigi
author_sort Spada, Martina
collection PubMed
description Cancer cells adjust their metabolism to meet energy demands. In particular, glutamine addiction represents a distinctive feature of several types of tumors, including colorectal cancer. In this study, four colorectal cancer cell lines (Caco-2, HCT116, HT29 and SW480) were cultured with or without glutamine. The growth and proliferation rate, colony-forming capacity, apoptosis, cell cycle, redox homeostasis and metabolomic analysis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT), flow cytometry, high-performance liquid chromatography and gas chromatography/mass spectrometry techniques. The results show that glutamine represents an important metabolite for cell growth and that its deprivation reduces the proliferation of colorectal cancer cells. Glutamine depletion induces cell death and cell cycle arrest in the GO/G1 phase by modulating energy metabolism, the amino acid content and antioxidant defenses. Moreover, the combined glutamine starvation with the glycolysis inhibitor 2-deoxy-D-glucose exerted a stronger cytotoxic effect. This study offers a strong rationale for targeting glutamine metabolism alone or in combination with glucose metabolism to achieve a therapeutic benefit in the treatment of colon cancer.
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spelling pubmed-100453052023-03-29 Glutamine Starvation Affects Cell Cycle, Oxidative Homeostasis and Metabolism in Colorectal Cancer Cells Spada, Martina Piras, Cristina Diana, Giulia Leoni, Vera Piera Frau, Daniela Virginia Serreli, Gabriele Simbula, Gabriella Loi, Roberto Noto, Antonio Murgia, Federica Caria, Paola Atzori, Luigi Antioxidants (Basel) Article Cancer cells adjust their metabolism to meet energy demands. In particular, glutamine addiction represents a distinctive feature of several types of tumors, including colorectal cancer. In this study, four colorectal cancer cell lines (Caco-2, HCT116, HT29 and SW480) were cultured with or without glutamine. The growth and proliferation rate, colony-forming capacity, apoptosis, cell cycle, redox homeostasis and metabolomic analysis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT), flow cytometry, high-performance liquid chromatography and gas chromatography/mass spectrometry techniques. The results show that glutamine represents an important metabolite for cell growth and that its deprivation reduces the proliferation of colorectal cancer cells. Glutamine depletion induces cell death and cell cycle arrest in the GO/G1 phase by modulating energy metabolism, the amino acid content and antioxidant defenses. Moreover, the combined glutamine starvation with the glycolysis inhibitor 2-deoxy-D-glucose exerted a stronger cytotoxic effect. This study offers a strong rationale for targeting glutamine metabolism alone or in combination with glucose metabolism to achieve a therapeutic benefit in the treatment of colon cancer. MDPI 2023-03-10 /pmc/articles/PMC10045305/ /pubmed/36978930 http://dx.doi.org/10.3390/antiox12030683 Text en © 2023 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
Spada, Martina
Piras, Cristina
Diana, Giulia
Leoni, Vera Piera
Frau, Daniela Virginia
Serreli, Gabriele
Simbula, Gabriella
Loi, Roberto
Noto, Antonio
Murgia, Federica
Caria, Paola
Atzori, Luigi
Glutamine Starvation Affects Cell Cycle, Oxidative Homeostasis and Metabolism in Colorectal Cancer Cells
title Glutamine Starvation Affects Cell Cycle, Oxidative Homeostasis and Metabolism in Colorectal Cancer Cells
title_full Glutamine Starvation Affects Cell Cycle, Oxidative Homeostasis and Metabolism in Colorectal Cancer Cells
title_fullStr Glutamine Starvation Affects Cell Cycle, Oxidative Homeostasis and Metabolism in Colorectal Cancer Cells
title_full_unstemmed Glutamine Starvation Affects Cell Cycle, Oxidative Homeostasis and Metabolism in Colorectal Cancer Cells
title_short Glutamine Starvation Affects Cell Cycle, Oxidative Homeostasis and Metabolism in Colorectal Cancer Cells
title_sort glutamine starvation affects cell cycle, oxidative homeostasis and metabolism in colorectal cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045305/
https://www.ncbi.nlm.nih.gov/pubmed/36978930
http://dx.doi.org/10.3390/antiox12030683
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