Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer

New therapies are needed to improve the low survival rates of patients with metastatic colon cancer. Evidence suggests that amino acid (AA) restriction can be used to target the altered metabolism of cancer cells. In this work, we evaluated the therapeutic potential of selective AA restriction in co...

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Autores principales: Jiménez-Alonso, Julio José, Guillén-Mancina, Emilio, Calderón-Montaño, José Manuel, Jiménez-González, Víctor, Díaz-Ortega, Patricia, Burgos-Morón, Estefanía, López-Lázaro, Miguel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412877/
https://www.ncbi.nlm.nih.gov/pubmed/36014884
http://dx.doi.org/10.3390/nu14163378
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author Jiménez-Alonso, Julio José
Guillén-Mancina, Emilio
Calderón-Montaño, José Manuel
Jiménez-González, Víctor
Díaz-Ortega, Patricia
Burgos-Morón, Estefanía
López-Lázaro, Miguel
author_facet Jiménez-Alonso, Julio José
Guillén-Mancina, Emilio
Calderón-Montaño, José Manuel
Jiménez-González, Víctor
Díaz-Ortega, Patricia
Burgos-Morón, Estefanía
López-Lázaro, Miguel
author_sort Jiménez-Alonso, Julio José
collection PubMed
description New therapies are needed to improve the low survival rates of patients with metastatic colon cancer. Evidence suggests that amino acid (AA) restriction can be used to target the altered metabolism of cancer cells. In this work, we evaluated the therapeutic potential of selective AA restriction in colon cancer. After observing anticancer activity in vitro, we prepared several artificial diets and evaluated their anticancer activity in two challenging animal models of metastatic colon cancer. These models were established by injecting CT26.WT murine colon cancer cells in the peritoneum (peritoneal dissemination) or in the tail vein (pulmonary metastases) of immunocompetent BALB/cAnNRj mice. Capecitabine, which is a first-line treatment for patients with metastatic colon cancer, was also evaluated in these models. Mice fed diet TC1 (a diet lacking 10 AAs) and diet TC5 (a diet with 6% casein, 5% glutamine, and 2.5% leucine) lived longer than untreated mice in both models; several mice survived the treatment. Diet TC5 was better than several cycles of capecitabine in both cancer models. Cysteine supplementation blocked the activity of diets TC1 and TC5, but cysteine restriction was not sufficient for activity. Our results indicated that artificial diets based on selective AA restriction have therapeutic potential for colon cancer.
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spelling pubmed-94128772022-08-27 Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer Jiménez-Alonso, Julio José Guillén-Mancina, Emilio Calderón-Montaño, José Manuel Jiménez-González, Víctor Díaz-Ortega, Patricia Burgos-Morón, Estefanía López-Lázaro, Miguel Nutrients Article New therapies are needed to improve the low survival rates of patients with metastatic colon cancer. Evidence suggests that amino acid (AA) restriction can be used to target the altered metabolism of cancer cells. In this work, we evaluated the therapeutic potential of selective AA restriction in colon cancer. After observing anticancer activity in vitro, we prepared several artificial diets and evaluated their anticancer activity in two challenging animal models of metastatic colon cancer. These models were established by injecting CT26.WT murine colon cancer cells in the peritoneum (peritoneal dissemination) or in the tail vein (pulmonary metastases) of immunocompetent BALB/cAnNRj mice. Capecitabine, which is a first-line treatment for patients with metastatic colon cancer, was also evaluated in these models. Mice fed diet TC1 (a diet lacking 10 AAs) and diet TC5 (a diet with 6% casein, 5% glutamine, and 2.5% leucine) lived longer than untreated mice in both models; several mice survived the treatment. Diet TC5 was better than several cycles of capecitabine in both cancer models. Cysteine supplementation blocked the activity of diets TC1 and TC5, but cysteine restriction was not sufficient for activity. Our results indicated that artificial diets based on selective AA restriction have therapeutic potential for colon cancer. MDPI 2022-08-17 /pmc/articles/PMC9412877/ /pubmed/36014884 http://dx.doi.org/10.3390/nu14163378 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
Jiménez-Alonso, Julio José
Guillén-Mancina, Emilio
Calderón-Montaño, José Manuel
Jiménez-González, Víctor
Díaz-Ortega, Patricia
Burgos-Morón, Estefanía
López-Lázaro, Miguel
Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer
title Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer
title_full Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer
title_fullStr Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer
title_full_unstemmed Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer
title_short Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer
title_sort artificial diets based on selective amino acid restriction versus capecitabine in mice with metastatic colon cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412877/
https://www.ncbi.nlm.nih.gov/pubmed/36014884
http://dx.doi.org/10.3390/nu14163378
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