Redox catalysts as sensitisers towards oxidative stress.

Abstract:

:The predominance of oxidative stress in many tumour cell environments provides a means to selectively target these cells via protein oxidation. The zinc fingers of transcription factors utilise cysteine thiols for structural zinc coordination. Redox control of DNA binding regulates transcription and therefore the overall rates of proliferation, apoptosis and necrosis in the carcinoma. We report here the adverse effects of glutathione peroxidase (GPx) mimics towards zinc finger motifs and PC12 cell survival. Nanomolar catalyst concentrations facilitated H2O2-induced oxidation of an Sp1 transcription factor fragment. In PC12 cells GPx catalysis triggered a significant increase in cell death, correlating with severity of oxidative stress. As a consequence, we conclude that GPx mimics are potential chemotherapeutic agents.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Giles NM,Gutowski NJ,Giles GI,Jacob C

doi

10.1016/s0014-5793(02)03890-5

keywords:

subject

Has Abstract

pub_date

2003-01-30 00:00:00

pages

179-82

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579302038905

journal_volume

535

pub_type

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