Caloric Restriction Enhances Chemotherapy Efficacy and Reshapes Stress Responses in Sarcoma
Jorddam Almondes Martins1, Irislene Costa Pereira1, Thiago Sousa Reinaldo1
1Metabolic Diseases, Exercise and Nutrition Group (DOMEN), Glauto Tuquarre Metabolic Diseases Laboratory (LabGT), Department of Biophysics and Physiology, Federal University of Piauí, Teresina 64049-550, PI, Brazil.
Cancers
|January 10, 2026
Summary
Caloric restriction combined with chemotherapy is safe and effective for cancer treatment. This nutritional strategy enhances antitumor efficacy and improves tolerance to chemotherapy by reducing side effects and DNA damage.
Area of Science:
- Oncology
- Nutritional Science
- Cancer Research
Background:
- Chemotherapy resistance remains a significant challenge in cancer treatment.
- Nutritional interventions, particularly caloric restriction, show promise in sensitizing tumors to therapy.
- Caloric restriction modulates tumor metabolism, potentially enhancing cancer cell sensitivity to conventional treatments.
Purpose of the Study:
- To evaluate the safety and efficacy of combining caloric restriction with chemotherapy.
- To investigate the effects on immunological, hematological, and oxidative stress parameters.
- To assess impacts on tumor and liver morphology and DNA damage in a Sarcoma-180 model.
Main Methods:
- Mice with Sarcoma-180 tumors were divided into four groups: Ad Libitum (AL), AL + Doxorubicin (ALDOX), Caloric Restriction (CR), and CR + Doxorubicin (CRDOX).
- Evaluated tumor weight/volume, food/caloric intake, hematotoxicity, lipid metabolism, oxidative stress markers, genotoxicity, morphology, and survival.
- Assessed peripheral blood and tumor tissue for various biomarkers and histological changes.
Main Results:
- The combination of caloric restriction and doxorubicin was safe, preserving body weight and avoiding metabolic disturbances.
- This regimen significantly reduced tumor volume and mass while mitigating doxorubicin-induced hematotoxicity.
- Chemotherapy-induced DNA damage was decreased in peripheral blood, indicating a systemic protective effect.
- Oxidative stress markers (NOx, MDA) were reduced, and antioxidant activity was enhanced in the tumor.
- Histological analysis revealed tumor cell death (apoptosis) and reduced local invasion.
Conclusions:
- Caloric restriction combined with doxorubicin is safe and well-tolerated in the Sarcoma-180 model.
- This combined approach enhances the antitumor efficacy of doxorubicin.
- Nutritional deprivation strategies can improve tolerance to chemotherapy and boost treatment outcomes.
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