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

• Published in: International journal of molecular sciences Vol. 23; no. 24; p. 16132
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17-12-2022; MDPI
• Subjects: Amino Acids; Angiogenesis; Animal models; Animals; Antiangiogenic agents; Antiangiogenics; Antitumor activity; Apoptosis; Artificial diets; cancer; cancer metabolism; Cancer therapies; cancer therapy; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Cytotoxicity; Diet; Drugs; Immune checkpoint inhibitors; Immunosuppressive agents; Immunotherapy; Kidney cancer; Kidney Neoplasms - pathology; Kinases; Lipids; Metastases; Metastasis; Methionine; Mice; Mutation; PD-1 protein; Peritoneum; renal adenocarcinoma; Renal cell carcinoma; Sunitinib - pharmacology; Sunitinib - therapeutic use; Survival; Vascular endothelial growth factor; cancer metabolism; kidney cancer; selective amino acid restriction therapy; cancer therapy; renal adenocarcinoma; metastasis; amino acids; restriction; renal cancer; cancer
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232416132

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.