Högskolan i Skövde

Pancreatic cancer remains one of the most aggressive malignancies, with limited treatment options and poor diagnosis. As cancer cells mostly depend on antioxidant defences to control reactive oxygen species levels, targeting redox homeostasis has emerged as a promising strategy. Selenite, a redox-active compound, alters cellular signalling pathways and induces oxidative stress, particularly in tumour cells. It also regulates the activation of selenoproteins, including glutathione peroxidase 4, an antioxidant enzyme that prevents lipid peroxidation. A key determinant of selenite uptake is the xCT antiporter, whose activity is tightly linked to glucose and glutamine metabolism through glutathione synthesis, thereby mitigating oxidative stress. Besides, the cellular response to metabolic conditions is highly dependent on time. This study aimed to explore how selenite toxicity depends on metabolic conditions and adaptation periods in pancreatic cancer cell lines, focusing on the role of glucose and glutamine availability. The selenite treatment of PANC-1 and HPAF-II cell lines were assessed using a cell proliferation assay, and the expression of glutathione peroxidase 4 was measured using Western blot. Selenite reduced the viability of both cell lines in a dose-dependent manner, with HPAF-II cells exhibiting greater sensitivity to the treatment. Metabolic conditions significantly influenced the efficacy of selenite in both cell lines, although the effects varied between them. However, the impact of the adaptation period on selenite response was less pronounced. These findings suggest that the metabolic state critically shapes the redox vulnerability of pancreatic cancer during selenite treatment, highlighting its potential for targeted cancer therapy.