Two-step mechanism of induction of the gene expression of a prototypic cancer-protective enzyme by diphenols.
Details
Serval ID
serval:BIB_00183B2C4048
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Two-step mechanism of induction of the gene expression of a prototypic cancer-protective enzyme by diphenols.
Journal
Chemical research in toxicology
ISSN
0893-228X (Print)
ISSN-L
0893-228X
Publication state
Published
Issued date
04/2008
Peer-reviewed
Oui
Volume
21
Number
4
Pages
805-812
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Cancer-preventive activity by exogenous molecules can be mediated by enhancing the expression of cytoprotective enzymes [e.g, glutathione- S-transferase (GST) or NAD(P)H-quinone oxidoreductase 1 (NQO1)] via antioxidant-response elements (AREs) present in the promoter regions of their genes. Previously, potency of induction of NQO1 has been linearly correlated with the ability to release an electron from different classes of inducers, including diphenols, phenylpropenoids, and flavonoids. In the present work, we focus on the induction of NQO1 by diphenols, which we consider as a model underlying the mechanisms of action of other phenolic inducers such as phenylpropenoids and flavonoids. A two-step mechanism of NQO1 activation is proposed involving (i) oxidation of diphenol inducers to their quinone derivatives and (ii) oxidation of two highly reactive thiol groups by these quinones of a protein involved in NQO1 induction. These two putative routes are supported by linear correlations between the inducer potencies and the redox properties of diphenols and of their corresponding quinones. The linear correlations demonstrate the possibility to predict the enhanced gene expression of enzymatic defenses by diphenols from quantum mechanical calculations (i) of the ability of diphenols to release electrons and (ii) of the electron affinity of their corresponding quinones.
Keywords
Adaptor Proteins, Signal Transducing/metabolism, Animals, Antineoplastic Agents, Cell Line, Cytoskeletal Proteins/metabolism, Gene Expression, Kelch-Like ECH-Associated Protein 1, Mice, NAD(P)H Dehydrogenase (Quinone), NADPH Dehydrogenase/genetics, NF-E2-Related Factor 2/metabolism, Oxidation-Reduction, Phenols/toxicity, Quantitative Structure-Activity Relationship, Reactive Oxygen Species/metabolism
Pubmed
Web of science
Create date
05/02/2018 14:56
Last modification date
20/08/2019 12:22