Targeting oxidative stress-related diseases: organochalcogen catalysts as redox sensitizers.

Abstract:

:Tumor cells proliferate under conditions of oxidative stress. A novel therapeutic approach would be to enhance the cellular effects of the reactive oxygen species formed under these conditions by supplementation with a redox catalyst. This provides a means to target and specifically destroy cancer cells via oxidation of redox-sensitive proteins, such as transcription factors, while leaving cells with a normal redox balance largely unaffected. We have previously reported a preliminary observation on the effects of pro-oxidant catalysts that enhance cancer cell death. This paper presents a detailed in vitro investigation into the mechanism of action of synthetic glutathione peroxidase mimics on a model Sp1 transcription factor peptide. The structure and redox potential of these mimics correlate with their ability to catalyze the oxidation of this zinc-binding motif by H(2)O(2) and these compounds promise therapeutic potential by promoting H(2)O(2)-induced PC12 cell death.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Giles NM,Giles GI,Holley JE,Gutowski NJ,Jacob C

doi

10.1016/s0006-2952(03)00544-6

subject

Has Abstract

pub_date

2003-11-15 00:00:00

pages

2021-8

issue

10

eissn

0006-2952

issn

1873-2968

pii

S0006295203005446

journal_volume

66

pub_type

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