Baicalein prevents capecitabine-induced heart damage in female Wistar rats and enhances its anticancer potential in MCF-7 breast cancer cells

Aim: We investigated the ability of baicalein (BAI) to enhance the anticancer potential of capecitabine (CAP) in the MCF-7 cell line and its protective effect on CAP-induced cardiotoxicity in female Wistar rats.Methods and key findings: In vitro study involved evaluating the effect of BAI and/or CAP on cell viability, cell cycle progression, and BAX and Bcl2 gene expression in MCF-7 cells. Co-treatment of BAI with CAP significantly reduced the viability of MCF-7 cells, improved their cytotoxic effect, markedly elevated the percentage of the sub-G1 population, drastically reduced the G2/M population, and significantly altered the mRNA expression of BAX and Bcl2 genes compared with each treatment alone. In vivo study revealed that the oral administration of CAP (140 mg/kg BW) to adult female rats significantly elevated the levels of serum creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 beta and cardiac TNF-alpha, IL-1 beta malondialdehyde (MDA) concentration, whereas it reduced the serum and cardiac total antioxidant capacity (TAC), level of cardiac glutathione (GSH) and activity of glutathione peroxidase (GPx) with a vast array of circulatory, inflammatory, degenerative, and necrotic alterations in the cardiac tissue. Furthermore, CAP administration significantly upregulated the mRNA expression of NF-kappa B, TLR4, MyD88, ATF6, CHOP, and JNK genes. Concurrent administration of BAI (200 mg/kg BW) and CAP significantly improved the biochemical al-terations and cardiac oxidant/antioxidant status and architecture. In addition, it modulated the TLR4/MyD88/ NF-kappa B pathway and endoplasmic reticulum stress.Significance: Altogether, BAI can augment the anticancer potential of CAP and alleviate its cardiotoxic effects during cancer treatment.

Automated summary

This study investigated the effects of baicalein (BAI) on enhancing the anticancer potential of capecitabine (CAP) in MCF-7 cells and its protective effect against CAP-induced cardiotoxicity in female Wistar rats. In vitro experiments showed that co-treatment of BAI with CAP significantly reduced cell viability, improved cytotoxicity, altered cell cycle progression, and affected the expression of BAX and Bcl2 genes. In vivo experiments revealed that CAP administration elevated cardiac markers and inflammatory cytokines, while reducing antioxidant capacity and causing cardiac tissue alterations. Simultaneous administration of BAI and CAP improved these alterations and modulated related pathways.