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Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothe...

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Autores principales: Calderón-Montaño, José Manuel, Guillén-Mancina, Emilio, Jiménez-Alonso, Julio José, Jiménez-González, Víctor, Burgos-Morón, Estefanía, Mate, Alfonso, Pérez-Guerrero, María Concepción, López-Lázaro, Miguel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783696/
https://www.ncbi.nlm.nih.gov/pubmed/36555771
http://dx.doi.org/10.3390/ijms232416132
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author Calderón-Montaño, José Manuel
Guillén-Mancina, Emilio
Jiménez-Alonso, Julio José
Jiménez-González, Víctor
Burgos-Morón, Estefanía
Mate, Alfonso
Pérez-Guerrero, María Concepción
López-Lázaro, Miguel
author_facet Calderón-Montaño, José Manuel
Guillén-Mancina, Emilio
Jiménez-Alonso, Julio José
Jiménez-González, Víctor
Burgos-Morón, Estefanía
Mate, Alfonso
Pérez-Guerrero, María Concepción
López-Lázaro, Miguel
author_sort Calderón-Montaño, José Manuel
collection PubMed
description Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we screened 18 artificial diets for anticancer activity in a challenging animal model of renal cell carcinoma. The model was established by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine, and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential and mechanism of action of this simple and inexpensive anticancer strategy.
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spelling pubmed-97836962022-12-24 Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma Calderón-Montaño, José Manuel Guillén-Mancina, Emilio Jiménez-Alonso, Julio José Jiménez-González, Víctor Burgos-Morón, Estefanía Mate, Alfonso Pérez-Guerrero, María Concepción López-Lázaro, Miguel Int J Mol Sci Article Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we screened 18 artificial diets for anticancer activity in a challenging animal model of renal cell carcinoma. The model was established by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine, and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential and mechanism of action of this simple and inexpensive anticancer strategy. MDPI 2022-12-17 /pmc/articles/PMC9783696/ /pubmed/36555771 http://dx.doi.org/10.3390/ijms232416132 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
Calderón-Montaño, José Manuel
Guillén-Mancina, Emilio
Jiménez-Alonso, Julio José
Jiménez-González, Víctor
Burgos-Morón, Estefanía
Mate, Alfonso
Pérez-Guerrero, María Concepción
López-Lázaro, Miguel
Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma
title Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma
title_full Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma
title_fullStr Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma
title_full_unstemmed Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma
title_short Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma
title_sort manipulation of amino acid levels with artificial diets induces a marked anticancer activity in mice with renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9783696/
https://www.ncbi.nlm.nih.gov/pubmed/36555771
http://dx.doi.org/10.3390/ijms232416132
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