Artificial Diets with Selective Restriction of Amino Acids and Very Low Levels of Lipids Induce Anticancer Activity in Mice with Metastatic Triple-Negative Breast Cancer

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show for the first time that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with...

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Main Authors: Emilio Guillén-Mancina, Julio José Jiménez-Alonso, José Manuel Calderón-Montaño, Víctor Jiménez-González, Patricia Díaz-Ortega, Estefanía Burgos-Morón, Miguel López-Lázaro
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/15/5/1540
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author Emilio Guillén-Mancina
Julio José Jiménez-Alonso
José Manuel Calderón-Montaño
Víctor Jiménez-González
Patricia Díaz-Ortega
Estefanía Burgos-Morón
Miguel López-Lázaro
author_facet Emilio Guillén-Mancina
Julio José Jiménez-Alonso
José Manuel Calderón-Montaño
Víctor Jiménez-González
Patricia Díaz-Ortega
Estefanía Burgos-Morón
Miguel López-Lázaro
author_sort Emilio Guillén-Mancina
collection DOAJ
description Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show for the first time that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were also tested in this model. AA manipulation led to modest improvements in mice survival when the levels of lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Some mice fed the artificial diets as monotherapy lived much longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.
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spelling doaj.art-77bb570feb55438ab1328f5bb4ebae032023-11-17T07:25:28ZengMDPI AGCancers2072-66942023-02-01155154010.3390/cancers15051540Artificial Diets with Selective Restriction of Amino Acids and Very Low Levels of Lipids Induce Anticancer Activity in Mice with Metastatic Triple-Negative Breast CancerEmilio Guillén-Mancina0Julio José Jiménez-Alonso1José 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, SpainPatients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show for the first time that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were also tested in this model. AA manipulation led to modest improvements in mice survival when the levels of lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Some mice fed the artificial diets as monotherapy lived much longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.https://www.mdpi.com/2072-6694/15/5/1540amino acidslipidsdietlow-fat dietcancer therapycancer metabolism
spellingShingle Emilio Guillén-Mancina
Julio José Jiménez-Alonso
José Manuel Calderón-Montaño
Víctor Jiménez-González
Patricia Díaz-Ortega
Estefanía Burgos-Morón
Miguel López-Lázaro
Artificial Diets with Selective Restriction of Amino Acids and Very Low Levels of Lipids Induce Anticancer Activity in Mice with Metastatic Triple-Negative Breast Cancer
Cancers
amino acids
lipids
diet
low-fat diet
cancer therapy
cancer metabolism
title Artificial Diets with Selective Restriction of Amino Acids and Very Low Levels of Lipids Induce Anticancer Activity in Mice with Metastatic Triple-Negative Breast Cancer
title_full Artificial Diets with Selective Restriction of Amino Acids and Very Low Levels of Lipids Induce Anticancer Activity in Mice with Metastatic Triple-Negative Breast Cancer
title_fullStr Artificial Diets with Selective Restriction of Amino Acids and Very Low Levels of Lipids Induce Anticancer Activity in Mice with Metastatic Triple-Negative Breast Cancer
title_full_unstemmed Artificial Diets with Selective Restriction of Amino Acids and Very Low Levels of Lipids Induce Anticancer Activity in Mice with Metastatic Triple-Negative Breast Cancer
title_short Artificial Diets with Selective Restriction of Amino Acids and Very Low Levels of Lipids Induce Anticancer Activity in Mice with Metastatic Triple-Negative Breast Cancer
title_sort artificial diets with selective restriction of amino acids and very low levels of lipids induce anticancer activity in mice with metastatic triple negative breast cancer
topic amino acids
lipids
diet
low-fat diet
cancer therapy
cancer metabolism
url https://www.mdpi.com/2072-6694/15/5/1540
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