Anti-cancer effect of palmitic acid against the endometrial cancer progression via inducing ferroptosis

Abstract

Background

The critical role of metabolic reprogramming as a potential therapeutic target in the management of endometrial cancer (EC) progression requires further investigation. This study investigated the anti-cancer effect of palmitic acid (PA) on EC progression using cellular and xenograft models, combined with integrated transcriptomic and metabolomic analyses to elucidate the molecular pathways through which PA induces ferroptosis and inhibits tumor growth.

Methods

The anti-cancer effects of PA were assessed through comprehensive in vitro assays, including cell viability, proliferation, migration, invasion, adhesion, clonogenicity, cell-cycle distribution, apoptosis, and epithelial-mesenchymal transition (EMT). In vivo, the therapeutic efficacy of PA was evaluated using a xenograft mouse model. Transcriptomic and metabolomic profiling identified differentially expressed genes (DEGs) and metabolites, with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses further exploring PA's mechanistic impact.

Results

PA significantly reduced the viability, migration, invasion, clonogenic potential, and EMT of EC cells, while inducing cell-cycle arrest and apoptosis. In xenograft models, PA effectively suppressed tumor growth. Mechanistically, transcriptomic and metabolomic analyses, together with changes in ferroptosis-related markers, indicated that PA exerts its anti-cancer effects at least in part through ferroptosis activation. This conclusion was further supported by multiple ferroptosis hallmarks and ferrostatin-1 rescue, which substantially attenuated PA-induced phenotypic and biochemical alterations.

Conclusion

PA suppressed EC progression by inducing ferroptosis, providing novel mechanistic insights into PA's anti-cancer properties and underscoring its potential as a therapeutic candidate for EC treatment.