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

## TL;DR

Palmitic acid inhibits endometrial cancer progression by inducing a type of cell death called ferroptosis, both in lab and animal models.

## Contribution

This study reveals that palmitic acid suppresses endometrial cancer through ferroptosis activation, offering a novel therapeutic strategy.

## Key findings

- Palmitic acid reduced cancer cell viability, migration, invasion, and epithelial-mesenchymal transition while inducing cell cycle arrest and apoptosis.
- In xenograft models, palmitic acid significantly suppressed tumor growth.
- Transcriptomic and metabolomic analyses confirmed that palmitic acid's anti-cancer effects are mediated through ferroptosis activation.

## Abstract

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.

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.

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.

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.

•PA 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.•PA exerts its anti-cancer effects primarily through the activation of ferroptosis.

PA 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.

PA exerts its anti-cancer effects primarily through the activation of ferroptosis.