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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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/16132 |
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| author | José Manuel Calderón-Montaño Emilio Guillén-Mancina Julio José Jiménez-Alonso Víctor Jiménez-González Estefanía Burgos-Morón Alfonso Mate María Concepción Pérez-Guerrero Miguel López-Lázaro |
| author_facet | José Manuel Calderón-Montaño Emilio Guillén-Mancina Julio José Jiménez-Alonso Víctor Jiménez-González Estefanía Burgos-Morón Alfonso Mate María Concepción Pérez-Guerrero Miguel López-Lázaro |
| author_sort | José Manuel Calderón-Montaño |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T16:18:57Z |
| format | Article |
| id | doaj.art-97ece2e4a0004d27855a4d38a90a45ae |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:18:57Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-97ece2e4a0004d27855a4d38a90a45ae2023-11-24T15:33:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241613210.3390/ijms232416132Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell CarcinomaJosé Manuel Calderón-Montaño0Emilio Guillén-Mancina1Julio José Jiménez-Alonso2Víctor Jiménez-González3Estefanía Burgos-Morón4Alfonso Mate5María Concepción Pérez-Guerrero6Miguel López-Lázaro7Department 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 Physiology, 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, SpainTargeted 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.https://www.mdpi.com/1422-0067/23/24/16132amino acidscancercancer metabolismcancer therapykidney cancerrenal adenocarcinoma |
| spellingShingle | José Manuel Calderón-Montaño Emilio Guillén-Mancina Julio José Jiménez-Alonso Víctor Jiménez-González Estefanía Burgos-Morón Alfonso Mate María Concepción Pérez-Guerrero Miguel López-Lázaro Manipulation of Amino Acid Levels with Artificial Diets Induces a Marked Anticancer Activity in Mice with Renal Cell Carcinoma International Journal of Molecular Sciences amino acids cancer cancer metabolism cancer therapy kidney cancer renal adenocarcinoma |
| 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 | amino acids cancer cancer metabolism cancer therapy kidney cancer renal adenocarcinoma |
| url | https://www.mdpi.com/1422-0067/23/24/16132 |
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