Publications

Palmitic acid, a saturated fatty acid, promotes cancer progression and induces endoplasmic reticulum stress, which is associated with a misfolded/unfolded protein response. The study aims to explore the impact of metabolic stress induced by palmitic acid on cell fate decisions in colon cancer cell HCT15, with a specific focus on PERK signalling that connects metabolic stress to senescence. In the MTT assay, the IC50 was determined to be 186 pM. The uptake of palmitic acid was confirmed by Oil Red O staining. Based on MTT and colony formation assays, the survival doses were identified as 50-100 pM, while lethal doses were determined to be 150-200 pM. Palmitic acid-induced oxidative stress is evidenced by increased ROS production, elevated MDA levels, and alterations in antioxidant activities. ER stress, driven by protein misfolding, was further confirmed through Thioflavin T staining. Gene expression analysis at survival doses revealed upregulation of ER stress and oxidative stress-related genes, including Bip, CHOP, PERK, ATF4, Nrf2, and HO-1, highlighting their role in promoting stress tolerance. Bioinformatics analysis of GEO datasets on senescence in HCT15 cells revealed a PERK-mediated pathway, supporting a link between palmitic acid-induced metabolic stress and senescence. This study emphasises the critical role of palmitic acid-induced ER stress in connecting metabolic stress to senescence in colon cancer cells and the involvement of PERK signalling as a key mediator in this process. These insights provide a deeper understanding of how metabolic stress contributes to senescence, potentially revealing new therapeutic targets for managing colon cancer progression.