Investigation of the effect of sapienic acid on the epidermal growth factor receptor (EGFR) pathway in colon cancer cells

Recent studies have focused increasingly on the influence of lipids on cancer development and apoptosis. Sapienic acid (SA), a monounsaturated fatty acid and a member of the ω-10 fatty acid family, has gained attention due to its potential regulatory effects on intracellular signaling pathways in cancer cells. Although alterations in lipid composition are known to modulate membrane receptor activation and downstream pathways, the impact of SA on the EGFR axis in colon cancer has not yet been systematically investigated. Therefore, this study aimed to examine the effects of SA on membrane-associated EGFR and its downstream signaling components. The cytotoxic effects of different SA concentrations were evaluated in the HCT116 colon cancer cell line using the MTT assay, and the IC50 value was determined. The magnitude of SA-induced oxidative stress was assessed spectrophotometrically through TAS and TOS measurements. Following incubation, total protein levels were quantified via the Bradford assay, and quantitative changes in EGFR activation were analyzed by Western blotting. Additionally, the long-term effects of SA on proliferative capacity were examined using a colony formation assay. In our experiments, the time-dependent effects of 50 µM SA on HCT116 cells were evaluated. Western blot results demonstrated that SA induced a biphasic response in the EGFR, AKT, and mTOR signaling pathways, characterized by early suppression followed by partial reactivation at later time points. Oxidative stress analyses revealed a strong yet transient oxidative response in the early phase, which diminished with prolonged incubation. Colony formation assays further showed that SA significantly reduced long-term cell survival and proliferative potential. Overall, these findings suggest that sapienic acid modulates proliferation dynamics and EGFR-mediated signaling in colon cancer cells and may represent a lipid-derived compound with potential anticancer properties.