FIGURE 2.

Schematic model for the potential of selenium on glioblastoma cells. The main purpose of the system X_C⁻ transporter is to supply cysteine for the production of the cellular antioxidant GSH. Selenide forms RSeS. Excessive Ca²⁺ influx through Se-induced oxidative stress causes an activation of TRP channels and mitochondrial membrane depolarization, leading to excessive ROS production. Thus, SEPHS2 is essential for survival in glioblastoma cells due to their elevated expression of system X_C⁻ transporter, which induces the import of Se compounds selenite and its conversion to toxic selenide resulting in selenide poisoning and cancer death. The increasing import of Se can be achieved by Se-containing nanoparticles. GLS is a key enzyme for glutaminolysis and bioenergy metabolism, which can be inhibited by selenite. Ca²⁺, calcium; Cys, cysteine; GLS, glutaminase; Glu, glutamate; Gln, glutamine; GSH, glutathione; GSSeSG, selenodiglutathione; GSSeH, selenoglutathione; SEPHS2, selenophosphate synthetase 2; ROS, reactive oxygen species; RSeS, reactive selenium species; Se, selenium compounds; TCA, tricarboxylic acid cycle; GPx4, glutathione peroxidase 4; TRP, transient receptor potential cationic channel; TRxR, thioredoxin reductase; SOD, superoxide dismutase.