title: Selenite and selenate inhibit human lymphocyte growth via different mechanisms.
abstract: Selenium compounds like selenite and selenate have strong inhibitory effects, particularly on mammalian tumor cell growth by unknown mechanisms. We found that the addition of sodium selenite and sodium selenate inhibited the growth of human 3B6 and BL41 lymphocytes. Selenite was more potent because 10 microM selenite produced a growth inhibitory effect similar to that of 250 microM selenate. The mechanism of action of selenite and selenate appears to be different. 3B6 and BL41 cells treated with selenite accumulated in the S-phase; however, selenate caused an accumulation of cells in G2. Selenite-mediated growth inhibition was irreversible, although the effects of selenate could be reversed. Selenite, in contrast to selenate, is efficiently reduced by the thioredoxin system (thioredoxin, thioredoxin reductase, and NADPH). At concentrations required to observe a similar effect on cell growth, the activity of thioredoxin reductase, recently shown to be a selenoprotein, increased in selenite-treated cells and decreased in selenate-treated cells. Ribonucleotide reductase activity was inhibited in an in vitro assay by selenite and selenodiglutathione but not by selenate. These results show that selenite and selenate use different mechanisms to inhibit cell growth.
authors.affiliation: The Medical Nobel Institute for Biochemistry, Department of Medical Biochemistry, Karolinska Institutet, Stockholm, Sweden. Giannis.Spyrou@mbb.ki.se
authors.forename: G
authors.initials: G
authors.lastname: Spyrou
authors.forename: M
authors.initials: M
authors.lastname: Björnstedt
authors.forename: S
authors.initials: S
authors.lastname: Skog
authors.forename: A
authors.initials: A
authors.lastname: Holmgren
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D012264:Ribonucleotide Reductases / Q000378:metabolism; D064586:Selenic Acid; D018036:Selenium Compounds / Q000494:pharmacology*; D018038:Sodium Selenite / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
chemical_list: D006131:Growth Inhibitors; D018036:Selenium Compounds; D012264:Ribonucleotide Reductases; D013880:Thioredoxin-Disulfide Reductase; D018038:Sodium Selenite; D064586:Selenic Acid