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Updated: Jun 18, 2025
A Preclinical Murine Model of Hepatic Metastases
Published on: September 27, 2014
A Diet Lacking Selenium, but Not Zinc, Copper or Manganese, Induces Anticancer Activity in Mice with Metastatic
Patricia Díaz-Ortega1, José Manuel Calderón-Montaño1, Julio José Jiménez-Alonso1
1Department of Pharmacology, Faculty of Pharmacy, University of Seville, 41012 Sevilla, Spain.
Abstract:
Selenium, zinc, copper, and manganese are essential components of antioxidant enzymes involved in the elimination of reactive oxygen species (ROS). Given that cancer cells produce high levels of ROS and the accumulation of ROS can lead to cell death, cancer cells may be susceptible to strategies that reduce ROS elimination. In this work, we prepared several artificial diets that contained normal carbohydrate, protein, and lipid levels but lacked selenium, zinc, copper, or manganese. The anticancer activity of these diets was examined in a metastatic ovarian cancer model, established by injecting ID8 Trp53-/- murine ovarian cancer cells into the peritoneal cavity of C57BL/6JRj mice. Treatments started 15 days later and consisted of replacing a normal diet with one of the artificial diets for several weeks. A significant improvement in mice survival was observed when the normal diet was replaced with the selenium-free diet. Diets lacking zinc, copper, or manganese showed no significant impact on mice survival. All diets were very well tolerated. The anticancer efficacy of a diet lacking selenium was confirmed in mice with metastatic colon cancer and in mice with metastatic triple-negative breast cancer. These results suggest that diets lacking selenium hold potential for the treatment of metastatic cancers.
Insights
Removing selenium from the diet significantly improved survival in mice with metastatic cancers. This dietary strategy, targeting reactive oxygen species elimination, shows promise for cancer treatment.
Area of Science:
- Oncology
- Nutritional Biochemistry
- Cancer Biology
Background:
- Antioxidant enzymes, crucial for eliminating reactive oxygen species (ROS), rely on essential minerals like selenium, zinc, copper, and manganese.
- Cancer cells exhibit high ROS levels, making them potentially vulnerable to strategies that impair ROS elimination.
Purpose of the Study:
- To investigate the anticancer potential of diets deficient in specific essential minerals (selenium, zinc, copper, manganese) in preclinical cancer models.
- To evaluate the impact of these mineral-deficient diets on survival rates and overall health in mice with metastatic cancers.
Main Methods:
- Preparation of artificial diets with normal macronutrient content but lacking individual essential minerals (selenium, zinc, copper, or manganese).
- Establishment of metastatic ovarian cancer models in mice by injecting ID8 Trp53-/- murine ovarian cancer cells.
- Administration of artificial diets to mice and monitoring of survival rates and diet tolerability.
Main Results:
- A selenium-free diet significantly improved survival in mice with metastatic ovarian cancer.
- Diets lacking zinc, copper, or manganese did not demonstrate a significant impact on survival.
- The anticancer efficacy of a selenium-deficient diet was further validated in metastatic colon and triple-negative breast cancer models.
- All tested artificial diets were well-tolerated by the mice.
Conclusions:
- Dietary selenium deficiency demonstrates significant anticancer efficacy against various metastatic cancers in preclinical models.
- Selenium-deficient diets represent a potential therapeutic strategy for managing metastatic cancers by modulating ROS levels.
- Further research is warranted to explore the clinical application of selenium-restricted diets in cancer therapy.
