4.7 Article

Redox proteome analysis of auranofin exposed ovarian cancer cells (A2780)

Journal

REDOX BIOLOGY
Volume 52, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.redox.2022.102294

Keywords

Redox proteomics; Cysteine; Auranofin; Gold drugs; Ovarian cancer

Funding

  1. ANR_AAP2019G project ERRED2 [197161]
  2. SESAME 2018 -Proteomics@PSL [EX039194]
  3. KBVU Grant [R146-A9414, R231-A13855]
  4. Associazione Italiana per la Ricerca sul Cancro (AIRC) Grant [IG20719]
  5. SESAME 2018 grant of the Conseil Regional d'Ile-de-France
  6. Higher Education Learning fellowship from the Erasmus + European program
  7. AIRC fellowship for Italy

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This study investigated the effects of Auranofin (AF) on protein expression and protein oxidation in A2780 cancer cells using a strategy based on simultaneous expression proteomics and redox proteomics determinations. The results demonstrated that AF affected the cellular redox state, mitochondrial functions, and induced ER stress, which were extensively validated. The study suggests that AF exerts its effects through a multitarget mechanism, mainly affecting redox metabolism and mitochondrial functions.
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.

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