Resveratrol as a cardioprotective adjuvant for 5-fluorouracil in the treatment of gastric cancer cells

• Published in: Brazilian journal of medical and biological research Vol. 57; p. e13537
• Main Authors: Liu, Lilong, Wang, Yexin, Dong, Yanyan, Lin, Shan, Guan, Wenhui, Song, Jia
• Format: Journal Article
• Language: English; Portuguese
• Published: Brazil Associação Brasileira de Divulgação Científica 01.01.2024
• Subjects: 5-Fluorouracil; Animals; Antimetabolites, Antineoplastic - pharmacology; Apoptosis; Apoptosis - drug effects; Autophagy - drug effects; BIOLOGY; Cardioctoxicity; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Fluorouracil - pharmacology; Humans; Male; MEDICINE, RESEARCH & EXPERIMENTAL; Mice; Myocytes, Cardiac - drug effects; Oxidative stress; Oxidative Stress - drug effects; p53; Resveratrol; Resveratrol - pharmacology; Resveratrol - therapeutic use; Stilbenes - pharmacology; Stilbenes - therapeutic use; Stomach Neoplasms - drug therapy; Stomach Neoplasms - pathology; Oxidative stress; Cardioctoxicity; 5-Fluorouracil; Resveratrol; Apoptosis; p53
• ISSN: 0100-879X; 1414-431X; 1414-431X
• DOI: 10.1590/1414-431X2024e13537

The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity.