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Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer
Julio José Jiménez-Alonso1, Emilio Guillén-Mancina1, José Manuel Calderón-Montaño1
1Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, Spain.
Abstract:
New therapies are needed to improve the low survival rates of patients with metastatic colon cancer. Evidence suggests that amino acid (AA) restriction can be used to target the altered metabolism of cancer cells. In this work, we evaluated the therapeutic potential of selective AA restriction in colon cancer. After observing anticancer activity in vitro, we prepared several artificial diets and evaluated their anticancer activity in two challenging animal models of metastatic colon cancer. These models were established by injecting CT26.WT murine colon cancer cells in the peritoneum (peritoneal dissemination) or in the tail vein (pulmonary metastases) of immunocompetent BALB/cAnNRj mice. Capecitabine, which is a first-line treatment for patients with metastatic colon cancer, was also evaluated in these models. Mice fed diet TC1 (a diet lacking 10 AAs) and diet TC5 (a diet with 6% casein, 5% glutamine, and 2.5% leucine) lived longer than untreated mice in both models; several mice survived the treatment. Diet TC5 was better than several cycles of capecitabine in both cancer models. Cysteine supplementation blocked the activity of diets TC1 and TC5, but cysteine restriction was not sufficient for activity. Our results indicated that artificial diets based on selective AA restriction have therapeutic potential for colon cancer.
Insights
Selective amino acid restriction via artificial diets shows promise for treating metastatic colon cancer. Specific diets extended survival in animal models, outperforming chemotherapy and offering new therapeutic avenues.
Area of Science:
- Oncology
- Nutritional Science
- Cancer Metabolism
Background:
- Metastatic colon cancer has poor survival rates, necessitating novel therapeutic strategies.
- Cancer cells exhibit altered metabolism, making them susceptible to targeted interventions like amino acid restriction.
- Amino acid metabolism plays a crucial role in cancer cell proliferation and survival.
Purpose of the Study:
- To investigate the therapeutic potential of selective amino acid restriction in colon cancer.
- To evaluate the efficacy of specially formulated artificial diets in preclinical models of metastatic colon cancer.
Main Methods:
- In vitro screening for anticancer activity of amino acid-restricted diets.
- Evaluation of artificial diets in murine models of peritoneal dissemination and pulmonary metastases (CT26.WT cells).
- Comparison of diet efficacy against capecitabine, a standard first-line treatment.
Main Results:
- Artificial diets TC1 (lacking 10 amino acids) and TC5 (specific amino acid composition) significantly improved survival in both metastatic models.
- Diet TC5 demonstrated superior efficacy compared to multiple cycles of capecitabine in both models.
- Cysteine supplementation abrogated the anticancer effects of diets TC1 and TC5, while cysteine restriction alone was insufficient.
Conclusions:
- Selective amino acid restriction using artificial diets represents a promising therapeutic strategy for metastatic colon cancer.
- Dietary interventions targeting amino acid metabolism offer a viable alternative or adjunct to conventional chemotherapy.
- Further research into specific amino acid dependencies and their modulation is warranted for colon cancer treatment.
