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...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2023-02-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/15/5/1540 |
_version_ | 1797615658104520704 |
---|---|
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. |
first_indexed | 2024-03-11T07:28:43Z |
format | Article |
id | doaj.art-77bb570feb55438ab1328f5bb4ebae03 |
institution | Directory Open Access Journal |
issn | 2072-6694 |
language | English |
last_indexed | 2024-03-11T07:28:43Z |
publishDate | 2023-02-01 |
publisher | MDPI AG |
record_format | Article |
series | Cancers |
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 |
work_keys_str_mv | AT emilioguillenmancina artificialdietswithselectiverestrictionofaminoacidsandverylowlevelsoflipidsinduceanticanceractivityinmicewithmetastatictriplenegativebreastcancer AT juliojosejimenezalonso artificialdietswithselectiverestrictionofaminoacidsandverylowlevelsoflipidsinduceanticanceractivityinmicewithmetastatictriplenegativebreastcancer AT josemanuelcalderonmontano artificialdietswithselectiverestrictionofaminoacidsandverylowlevelsoflipidsinduceanticanceractivityinmicewithmetastatictriplenegativebreastcancer AT victorjimenezgonzalez artificialdietswithselectiverestrictionofaminoacidsandverylowlevelsoflipidsinduceanticanceractivityinmicewithmetastatictriplenegativebreastcancer AT patriciadiazortega artificialdietswithselectiverestrictionofaminoacidsandverylowlevelsoflipidsinduceanticanceractivityinmicewithmetastatictriplenegativebreastcancer AT estefaniaburgosmoron artificialdietswithselectiverestrictionofaminoacidsandverylowlevelsoflipidsinduceanticanceractivityinmicewithmetastatictriplenegativebreastcancer AT miguellopezlazaro artificialdietswithselectiverestrictionofaminoacidsandverylowlevelsoflipidsinduceanticanceractivityinmicewithmetastatictriplenegativebreastcancer |