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Gold(III)-Dithiocarbamato Complexes Induce Cancer Cell Death Triggered by Thioredoxin Redox System Inhibition and Activation of ERK Pathway
- Source :
- Chemistry & Biology. (10):1128-1139
- Publisher :
- Elsevier Ltd.
-
Abstract
- Summary Although gold compounds are now recognized as promising anticancer agents, so far only gold(I) derivatives have been investigated for this purpose, whereas the use of gold(III) complexes has been hampered by their poor stability under physiological conditions. We have therefore carried out studies on selected gold(III) anticancer agents, showing enhanced stability due to the presence of chelating dithiocarbamato ligands. We found that they induce cancer cell death through both apoptotic and nonapoptotic mechanisms. They also inhibit thioredoxin reductase activity, generate free radicals, modify some mitochondrial functions, and increase ERK1/2 phosphorylation. Based on our results, we propose and discuss a working model suggesting that deregulation of the thioredoxin reductase/thioredoxin redox system is a major mechanism involved in the anticancer activity of the investigated gold(III)-dithiocarbamato complexes.
- Subjects :
- MAPK/ERK pathway
Thioredoxin-Disulfide Reductase
Time Factors
Free Radicals
Thioredoxin reductase
Clinical Biochemistry
Antineoplastic Agents
Biology
Ligands
Biochemistry
gold(III)-dithiocarbamato complexes
thioredoxin redox system
ERK pathway
mitochondrial permeability
PARP analysis
Thioredoxins
Gold Compounds
Thiocarbamates
Cell Line, Tumor
Drug Discovery
Tumor Cells, Cultured
Animals
Humans
Chelation
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Molecular Biology
Pharmacology
Cell Death
General Medicine
Cell biology
Mitochondria
Rats
CHEMBIO
Apoptosis
SIGNALING
Cancer cell
Molecular Medicine
Electrophoresis, Polyacrylamide Gel
CELLBIO
Thioredoxin
Organogold Compounds
Oxidation-Reduction
Subjects
Details
- Language :
- English
- ISSN :
- 10745521
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Chemistry & Biology
- Accession number :
- edsair.doi.dedup.....4d30540f6e3229de1c149db32749ad88
- Full Text :
- https://doi.org/10.1016/j.chembiol.2007.08.016