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Updated: Sep 28, 2025
Profiling Thiol Redox Proteome Using Isotope Tagging Mass Spectrometry
Published on: March 24, 2012
Redox proteome analysis of auranofin exposed ovarian cancer cells (A2780)
Giovanni Chiappetta1, Tania Gamberi2, Fiorella Faienza3
1Biological Mass Spectrometry and Proteomics Group, SMBP, PDC CNRS UMR, 8249, ESPCI Paris, Université PSL, 10 rue Vauquelin, 75005, Paris, France.
Abstract:
The effects of Auranofin (AF) on protein expression and protein oxidation in A2780 cancer cells were investigated through a strategy based on simultaneous expression proteomics and redox proteomics determinations. Bioinformatics analysis of the proteomics data supports the view that the most critical cellular changes elicited by AF treatment consist of thioredoxin reductase inhibition, alteration of the cell redox state, impairment of the mitochondrial functions, metabolic changes associated with conversion to a glycolytic phenotype, induction of ER stress. The occurrence of the above cellular changes was extensively validated by performing direct biochemical assays. Our data are consistent with the concept that AF produces its effects through a multitarget mechanism that mainly affects the redox metabolism and the mitochondrial functions and results into severe ER stress. Results are discussed in the context of the current mechanistic knowledge existing on AF.
Insights
Auranofin (AF) impacts cancer cell protein expression and oxidation by inhibiting thioredoxin reductase and disrupting mitochondrial function, leading to severe ER stress. This multitarget mechanism reveals AF
Area of Science:
- Biochemistry
- Cell Biology
- Proteomics
Background:
- Auranofin (AF) is an anti-rheumatic drug with demonstrated anticancer properties.
- The precise molecular mechanisms underlying AF's anticancer effects require further elucidation.
Purpose of the Study:
- To investigate the effects of Auranofin (AF) on protein expression and oxidation in A2780 cancer cells.
- To elucidate the multitarget mechanisms of AF action in cancer cells.
Main Methods:
- Simultaneous expression proteomics and redox proteomics.
- Bioinformatics analysis of proteomics data.
- Direct biochemical assays for validation.
Main Results:
- AF treatment inhibits thioredoxin reductase.
- AF alters the cellular redox state and impairs mitochondrial function.
- AF induces metabolic changes towards a glycolytic phenotype and causes ER stress.
Conclusions:
- AF exerts its anticancer effects through a multitarget mechanism.
- Key targets include redox metabolism and mitochondrial function, leading to severe ER stress.
- Understanding these mechanisms provides insights into AF's therapeutic potential.
