Selenium and cancer chemoprevention: hypotheses integrating the actions of selenoproteins and selenium metabolites in epithelial and non-epithelial target cells.
The trace element nutrient selenium (Se) discharges its well-known nutritional antioxidant activity through the Se-dependent glutathione peroxidases. It also regulates nuclear factor activities by redox mechanisms through the selenoprotein thioredoxin reductases. Converging data from epidemiological, ecological, and clinical studies have shown that Se can decrease the risk for some types of human cancers, especially those of the prostate, lung, and colon. Mechanistic studies have indicated that the methylselenol metabolite pool has many desirable attributes of chemoprevention, targeting both cancer cells and vascular endothelial cells, whereas the hydrogen selenide pool in excess of selenoprotein synthesis can lead to DNA single strand breaks, which may be mediated by some reactive oxygen species. We propose a new paradigm based on a consideration of the post-initiation biology of avascular early lesion expansion microenvironment, physiochemistry of Se delivery, and the obligatory need for angiogenesis to sustain lesion progression. Our model integrates the roles of selenoproteins and specific Se metabolites to account for cancer risk reduction or enhancement. For future studies, speciation (profiling) methods for Se metabolites and for Se forms in foods and supplements are much needed for hypothesis testing and for the development of mechanism-based Se status markers for cancer prevention. Randomized cancer prevention trials are necessary to test the efficacy of methyl selenium compounds.
Lü
Junxuan
J
Hormel Institute, University of Minnesota, Austin, MN 55912, USA. jlu@hi.umn.edu
Jiang
Cheng
C
D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000517:prevention & control*; D010084:Oxidation-Reduction / Q000187:drug effects; D014176:Protein Biosynthesis; D012643:Selenium / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D051140:Selenoproteins / Q000378:metabolism*
D051140:Selenoproteins; D012643:Selenium