Methods for accurate and reproducible studies of pharmacological effects of selenium in cancer

Abstract

Selenium compounds have pronounced effects on cell growth and proliferation. Nutritional levels induce selenoproteins. However, the antineoplastic effects of supra-nutritional selenium levels are not mediated by selenoproteins. The most studied compound, selenite, was shown in a clinical trial to possess extraordinary pharmacological properties. The uptake of selenite as for GS-Se-SG and selenocystine is dependent on the extracellular reducing environment maintained by the X_c^- cystine transporter (x_c^- antiporter) ensuring a high level of extracellular cysteine. The expression of the x_c^- antiporter is vital for selenium cytotoxicity and any xenobiotic or media constituents modulating the expression of this antiporter will greatly affect the cellular response. Cytotoxicity determinations are often difficult to interpret and repeat due to differences in culture conditions. In the current chapter, factors influencing the cellular response, e.g., media composition, cell culturing conditions, assays for key enzymes of importance for selenium metabolism and effects, along with selenium mediated modulation of microRNA expression and immune responses are treated.

Keywords: Cell culture media; Cellular thiols; Immune regulation; MicroRNA; Se-methylselenocysteine; Selenite; Selenium metabolizing enzyme; Selenoprotein; Thioredoxin system.