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

Autor:	Hatem E; Institut Curie, PSL Research University, CNRS UMR 3348, Université Paris-Saclay, 91405 Orsay, France., El Banna N; Institut Curie, PSL Research University, CNRS UMR 3348, Université Paris-Saclay, 91405 Orsay, France., Heneman-Masurel A; Institut Curie, PSL Research University, CNRS UMR 3348, Université Paris-Saclay, 91405 Orsay, France., Baïlle D; Institut Curie, PSL Research University, CNRS UMR 3348, Université Paris-Saclay, 91405 Orsay, France., Vernis L; Institut Curie, PSL Research University, CNRS UMR 3348, Université Paris-Saclay, 91405 Orsay, France.; Université Paris-Saclay, CNRS UPR 2301, Institut de Chimie des Substances Naturelles, 91198 Gif-sur-Yvette, France., Riquier S; Université Paris-Saclay, CNRS UPR 2301, Institut de Chimie des Substances Naturelles, 91198 Gif-sur-Yvette, France., Golinelli-Cohen MP; Université Paris-Saclay, CNRS UPR 2301, Institut de Chimie des Substances Naturelles, 91198 Gif-sur-Yvette, France., Guittet O; Université Paris-Saclay, CNRS UPR 2301, Institut de Chimie des Substances Naturelles, 91198 Gif-sur-Yvette, France., Vallières C; Université Paris-Saclay, CNRS UPR 2301, Institut de Chimie des Substances Naturelles, 91198 Gif-sur-Yvette, France., Camadro JM; Université Paris Cité, CNRS, Institut Jacques Monod, 75013 Paris, France., Qiu X; NanoBioPhotonics (nanofret.com), Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CNRS, CEA, 91400 Orsay, France., Hildebrandt N; NanoBioPhotonics (nanofret.com), Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CNRS, CEA, 91400 Orsay, France.; Laboratoire Chimie Organique, Bioorganique, Réactivité et Analyse (COBRA), Université de Rouen Normandie, CNRS, INSA, 76821 Mont-Saint-Aignan, France., Lepoivre M; Université Paris-Saclay, CNRS UPR 2301, Institut de Chimie des Substances Naturelles, 91198 Gif-sur-Yvette, France., Huang ME; Institut Curie, PSL Research University, CNRS UMR 3348, Université Paris-Saclay, 91405 Orsay, France.; Université Paris-Saclay, CNRS UPR 2301, Institut de Chimie des Substances Naturelles, 91198 Gif-sur-Yvette, France.
Jazyk:	angličtina
Zdroj:	Cancers [Cancers (Basel)] 2022 Oct 05; Vol. 14 (19). Date of Electronic Publication: 2022 Oct 05.
DOI:	10.3390/cancers14194864
Abstrakt:	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.
Databáze:	MEDLINE
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