Susceptibility of the antioxidant selenoenyzmes thioredoxin reductase and glutathione peroxidase to alkylation-mediated inhibition by anticancer acylfulvenes.

ABSTRACT: Selenium, in the form of selenocysteine, is a critical component of some major redox-regulating enzymes, including thioredoxin reductase (TrxR) and glutathione peroxidase (Gpx). TrxR has emerged as an anticancer target for drug development due to its elevated expression level in many aggressive human tumors. Acylfulvenes (AFs) are semisynthetic derivatives of the natural product illudin S and display improved cytotoxic selectivity profiles. AF and illudin S alkylate cellular macromolecules. Compared to AFs, illudin S more readily reacts with thiol-containing small molecules such as cysteine, glutathione, and cysteine-containing peptides. However, a previous study indicates that the reactivity of AFs and illudin S with glutathione reductase, a thiol-containing enzyme, is inversely correlate

SUBMITTER: Liu X 

PROVIDER: S-EPMC3210965 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature