Dados do Resumo

Título

CALORIC RESTRICTION SHOWED SINERGISTIC EFFECTS TO THE CHEMOTHERAPY AND IMPROVED SYSTEMIC HEALTH MARKERS OF SARCOMA-BEARING MICE

Introdução

Cancer remains a challenge due to its high incidence, with 704,000 new cases estimated in Brazil between 2023 and 2025. Some reports have indicated caloric restriction (CR) brings benefits, increased life expectancy, and delays carcinogenesis of carcinomas.

Objetivo

This study investigated how CR combined with chemotherapy influences chemotherapy antitumor activity, oxidative stress, antioxidant action, lipid profile, liver functions, survival, and gene signatures associated with sarcoma metabolism.

Métodos

Swiss mice bearing Sarcoma-180 were used to assess the impact of CR on the efficiency and selectivity of chemotherapy (CEUA/UFPI #752/2022). The protocol involved a 40% caloric restriction and intraperitoneal administration of doxorubicin (2 mg/g). It was assessed animal and tumor development, serum biochemical analyses [gamma-glutamyl transferase (GGT), glutamic-pyruvic transaminase (GPT), and oxaloacetic transaminase (GOT) activities, lipid profile, triglycerides, total cholesterol, high-density (HDL) and low-density lipoproteins (LDL)], as well as a complete blood count. For oxidative stress markers, it was measured NADPH oxidase (NOX), malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH) and superoxide dismutase (SOD) in tumor tissues. Moreover, genotoxicity was analyzed by comet assay in peripherical blood cells, tumors and livers were examined for morphological changes, survival testing, and metabolic gene expression.

Resultados

All groups subjected to CR showed no significant differences in body weight or hepatosomatic index compared to the control. However, CR alone and in combination with chemotherapy improved antitumor activity, reducing tumor mass and volume and increasing the tumor growth inhibition rate. CR also reduced the lipid profile, highlighting its contribution to improved cardiometabolic parameters. We observed a reduction in NOX, MDA, and GSH levels, along with an increase in SOD activity, underscoring CR's impact on regulating antioxidant defenses. CR also acted as a protective agent against chemotherapy-induced toxicity, preserving blood cells, controlling cellular invasion, promoting apoptosis and immune response, and increasing life expectancy by 80%. Additionally, it modulated gene signatures related to tumor metabolism, with overexpression of Mmp12 and Mmp13, and underexpression of Mustn1, Mybpc2, and Ankrd23

Conclusões

This study offers a new perspective on cancer treatment, highlighting CR as a promising strategy that not only delays tumor growth but also optimizes chemotherapy efficacy, regardless of dietary composition. CR promotes the maintenance of healthy cells, a crucial factor in clinical practice, and supports its potential as a viable approach to cancer treatment, warranting further investigation for clinical use.

Financiador do resumo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Palavras Chave

Caloric restriction; Câncer; sarcoma-180