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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MDPI AG
2022-08-01
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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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issn | 2072-6643 |
language | English |
last_indexed | 2024-03-09T04:00:56Z |
publishDate | 2022-08-01 |
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series | Nutrients |
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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