Targeting oxidative stress-related diseases: organochalcogen catalysts as redox sensitizers.
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.
School of Biological and Chemical Sciences, University of Exeter, Stocker Road, EX4 4QD, Exeter, UK.
Niroshini M
NM
Giles
Gregory I
GI
Giles
Janet E
JE
Holley
Nick J
NJ
Gutowski
Claus
C
Jacob
D000818:Animals; D002384:Catalysis; D018011:Chalcogens / Q000494:pharmacology*; D004563:Electrochemistry; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D015032:Zinc / Q000378:metabolism; D016335:Zinc Fingers / Q000187:drug effects / Q000502:physiology
D018011:Chalcogens; D006861:Hydrogen Peroxide; D015032:Zinc