Induction of Complementary Function Reductase Enzymes in Colon Cancer Cells by Dithiole-3-thione versus Sodium Selenite

Erzinger et al., J Biochem Mol Toxicol. (2014) - PMID: 25179160

Product(s) used in this publication:  SpikeTides™ - Proteomics Peptide Standards

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

NAD(P)H:

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.

© 2014 Wiley Periodicals, Inc.

KEYWORDS:

Biotransformation Efficiency; Enzyme Activity; Enzyme Induction; Quantitative Proteomics; Reductase

Stay in touch and be the first to receive the latest news!