Submitted to: Current Opinion in Clinical Nutrition and Metabolic Care
Publication Type: Review Article
Publication Acceptance Date: July 30, 2008
Publication Date: August 1, 2008
Citation: Combs, G.F., Jackson, M.I. 2008. Selenium and Anticarcinogenesis: Underlying Mechanisms. Current Opinion in Clinical Nutrition and Metabolic Care. 11:718-726. Technical Abstract: The manuscript discusses recent research related to anticarcinogenic mechanisms of selenium (Se) action in light of the underlying chemical/biochemical functions of the selenium species likely to be executors of those effects. Recent studies in a variety of model systems have increased understanding of the anticarcinogenic mechanisms of Se-compounds. These include effects on gene expression, DNA damage and repair, signaling pathways, regulation of cell cycle and apoptosis, metastasis and angiogenesis. These effects would appear to be related to the production of reactive oxygen species produced by the redox cycling, modification of protein-thiols, and methionine mimicry. Three principle Se-metabolites appear to execute these effects: hydrogen selenide, methylselenol and selenomethionine. That various Se-compounds can be metabolized to one or more of these species but differ in anticarcinogenic activity indicates competing pathways of their metabolic and chemical/biochemical disposition. Increasing knowledge of selenoprotein polymorphisms has shown that at least some are related to cancer risk and may affect carcinogenesis indirectly by influencing Se-metabolism. The anticarcinogenic effects of Se-compounds constitute intermediate mechanisms with several underlying chemical/biochemical mechanisms: redox cycling, alteration of protein thiol redox status and methionine mimicry.