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Inhibition of Thioredoxin Reductase by Triosmium Carbonyl Clusters
- Source :
- Chemical Research in Toxicology. 33:2441-2445
- Publication Year :
- 2020
- Publisher :
- American Chemical Society (ACS), 2020.
-
Abstract
- Tumor cells are characterized by increased reactive oxygen species production in parallel with an enhanced antioxidant system to avoid oxidative damage. The inhibition of antioxidant systems is an effective way to kill cancer cells, and the thioredoxin system or, more specifically, the cytosolic selenocysteine-containing enzyme thioredoxin reductase (TrxR) has become an interesting target for cancer therapy. We show here that the known cytotoxic and apoptosis-inducing osmium carbonyl cluster Os3(CO)10(NCCH3)2 (1) is a nonsubstrate inhibitor of mammalian TrxR, with an IC50 of 5.3 ± 0.9 μM. It inhibits TrxR selectively over the closely related glutathione reductase (GR) and in the presence of excess reduced glutathione (GSH). This inhibition has also been demonstrated in cell lysates, suggesting that TrxR inhibition is a potential apoptotic pathway for 1.
- Subjects :
- Thioredoxin-Disulfide Reductase
Antioxidant
medicine.medical_treatment
Thioredoxin reductase
Glutathione reductase
Antineoplastic Agents
010501 environmental sciences
Toxicology
01 natural sciences
03 medical and health sciences
chemistry.chemical_compound
Coordination Complexes
Cell Line, Tumor
medicine
Humans
Enzyme Inhibitors
Cell Proliferation
030304 developmental biology
0105 earth and related environmental sciences
chemistry.chemical_classification
0303 health sciences
Molecular Structure
Chemistry
General Medicine
Glutathione
Osmium
Cytosol
Enzyme
Biochemistry
Cancer cell
Female
Drug Screening Assays, Antitumor
Thioredoxin
Subjects
Details
- ISSN :
- 15205010 and 0893228X
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Chemical Research in Toxicology
- Accession number :
- edsair.doi.dedup.....ba1ca2ba2d9136236c686fc3f026c66f