title: Induction of complementary function reductase enzymes in colon cancer cells by dithiole-3-thione versus sodium selenite.
abstract: Cellular induction of reductase enzymes can alter the susceptibility of cells toward drugs and chemicals. In this study, we compared the capacity of a single dose of sodium selenite and 3H-1,2-dithiole-3-thione (D3T) to influence the drug-relevant reducing capacity of HT29 cells over time, and defined the protein-specific contribution to this activity on the basis of selected reaction monitoring mass spectrometry. Thioredoxin reductase 1 (TrxR1) protein levels and activity were inducible up to 2.2-fold by selenium. In contrast, selenium had only a minor influence on prostaglandin reductase 1 (PTGR1) and
  quinone oxidoreductase 1 (NQO1) activity and protein levels. D3T, a strong Nrf2 inducer, induced all the reductases and additionally increased the cytotoxicity of hydroxymethylacylfulvene, a bioreductive DNA-alkylating drug. The data and experimental approaches allow one to define induction potency for reductase enzymes PTGR1, TrxR1, and NQO1 in HT29 cells and link these to changes in drug cytotoxicity.
authors.affiliation: Department of Health Sciences and Technology, Institute of Food, Nutrition and Health, ETH Zurich, 8092, Zurich, Switzerland.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Erzinger
authors.forename: Cédric
authors.initials: C
authors.lastname: Bovet
authors.forename: Anuli
authors.initials: A
authors.lastname: Uzozie
authors.forename: Shana J
authors.initials: SJ
authors.lastname: Sturla
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D018038:Sodium Selenite / Q000494:pharmacology*; D013871:Thiones / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D054481:Thioredoxin Reductase 1 / Q000096:biosynthesis*; D014131:Trace Elements / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009363:Neoplasm Proteins; D013871:Thiones; D013876:Thiophenes; D014131:Trace Elements; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D018038:Sodium Selenite; C049325:1,2-dithiol-3-thione
keywords: Biotransformation Efficiency; Enzyme Activity; Enzyme Induction; Quantitative Proteomics; Reductase