Novel Insights into Redox-Based Mechanisms for Auranofin-Induced Rapid Cancer Cell Death - Normandie Université Access content directly
Journal Articles Cancers Year : 2022

Novel Insights into Redox-Based Mechanisms for Auranofin-Induced Rapid Cancer Cell Death

Elie Hatem
Nadine El Banna
  • Function : Author
Amélie Heneman-Masurel
  • Function : Author
Dorothée Baïlle
Laurence Vernis
  • Function : Author
Sylvie Riquier
  • Function : Author
Marie-Pierre Golinelli-Cohen
Olivier Guittet
  • Function : Author
Cindy Vallières
  • Function : Author
Jean-Michel Camadro
Xue Qiu
Michel Lepoivre
  • Function : Author
Meng-Er Huang

Abstract

Auranofin (Ridaura®, AUF) is a gold complex originally approved as an antirheumatic agent that has emerged as a potential candidate for multiple repurposed therapies. The best-studied anticancer mechanism of AUF is the inhibition of thioredoxin reductase (TrxR). However, a number of reports indicate a more complex and multifaceted mode of action for AUF that could be cancer cell type- and dose-dependent. In this study, we observed that AUF displayed variable cytotoxicity in five triple-negative breast cancer cell lines. Using representative MDA-MB-231 cells treated with moderate and cytotoxic doses of AUF, we evidenced that an AUF-mediated TrxR inhibition alone may not be sufficient to induce cell death. Cytotoxic doses of AUF elicited rapid and drastic intracellular oxidative stress affecting the mitochondria, cytoplasm and nucleus. A “redoxome” proteomics investigation revealed that a short treatment with a cytotoxic dose AUF altered the redox state of a number of cysteines-containing proteins, pointing out that the cell proliferation/cell division/cell cycle and cell–cell adhesion/cytoskeleton structure were the mostly affected pathways. Experimentally, AUF treatment triggered a dose-dependent S-phase arrest and a rapid disintegration of the actin cytoskeleton structure. Our study shows a new spectrum of AUF-induced early effects and should provide novel insights into the complex redox-based mechanisms of this promising anticancer molecule.

Dates and versions

hal-03814453 , version 1 (14-10-2022)

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Elie Hatem, Nadine El Banna, Amélie Heneman-Masurel, Dorothée Baïlle, Laurence Vernis, et al.. Novel Insights into Redox-Based Mechanisms for Auranofin-Induced Rapid Cancer Cell Death. Cancers, 2022, 14 (19), pp.4864. ⟨10.3390/cancers14194864⟩. ⟨hal-03814453⟩
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