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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Main Authors: Julio José Jiménez-Alonso, Emilio Guillén-Mancina, José Manuel Calderón-Montaño, Víctor Jiménez-González, Patricia Díaz-Ortega, Estefanía Burgos-Morón, Miguel López-Lázaro
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/16/3378
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author Julio José Jiménez-Alonso
Emilio Guillén-Mancina
José Manuel Calderón-Montaño
Víctor Jiménez-González
Patricia Díaz-Ortega
Estefanía Burgos-Morón
Miguel López-Lázaro
author_facet Julio José Jiménez-Alonso
Emilio Guillén-Mancina
José Manuel Calderón-Montaño
Víctor Jiménez-González
Patricia Díaz-Ortega
Estefanía Burgos-Morón
Miguel López-Lázaro
author_sort Julio José Jiménez-Alonso
collection DOAJ
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 doaj.art-e94053aee8504e9d8685babece1521192023-12-03T14:14:37ZengMDPI AGNutrients2072-66432022-08-011416337810.3390/nu14163378Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon CancerJulio José Jiménez-Alonso0Emilio Guillén-Mancina1José Manuel Calderón-Montaño2Víctor Jiménez-González3Patricia Díaz-Ortega4Estefanía Burgos-Morón5Miguel López-Lázaro6Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, SpainDepartment of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, SpainDepartment of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, SpainDepartment of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, SpainDepartment of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, SpainDepartment of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, SpainDepartment of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, SpainNew 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.https://www.mdpi.com/2072-6643/14/16/3378anticancer activitycolorectal cancermetastasisselective amino acid restriction therapycancer metabolismamino acids
spellingShingle Julio José Jiménez-Alonso
Emilio Guillén-Mancina
José Manuel Calderón-Montaño
Víctor Jiménez-González
Patricia Díaz-Ortega
Estefanía Burgos-Morón
Miguel López-Lázaro
Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer
Nutrients
anticancer activity
colorectal cancer
metastasis
selective amino acid restriction therapy
cancer metabolism
amino acids
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 anticancer activity
colorectal cancer
metastasis
selective amino acid restriction therapy
cancer metabolism
amino acids
url https://www.mdpi.com/2072-6643/14/16/3378
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