Are Selenoproteins Important for the Cancer Protective Effects of Selenium?

Epidemiologic and preclinical studies provide evidence that the essential nutrient selenium has cancer protective properties. The mammalian genome encodes 25 selenoprotein genes that contain one or more molecules of selenium in the form of the amino acid selenocysteine, which is translationally inserted into the growing peptide at the UGA codon. Most of the known metabolic functions of selenium are associated with these selenoprotens, and there is evidence that polymorphisms in some selenoproteins, may be associated with increased cancer risk. However, it is not currently known whether selenoproteins or low molecular weight selenium compounds mediate the cancer protective effects of dietary selenium. The anti-carcinogenic effects of selenium occur at much greater levels of intake than is necessary to maximize glutathione peroxidase activity, while thioredoxin reductase activity can be influenced by supranutritional levels of intake. Also, there is increasing evidence that many of the putative effects of selenium on cell cycle control and apoptosis are mediated via reactive oxygen species, and intracellular reactive oxygen species are regulated by several selenoproteins. The development of transgenic and knockout mice with altered selenoprotein expression provides a model system to evaluate the importance of selenoproteins in mediating the cancer protective effects of selenium.