On the binding of auranofin to Prdx6 and its potential role in cancer cell sensitivity to treatment

In this study, we demonstrate that ferroptosis is a component of the cell death mechanism induced by auranofin in HT-1080 cells, in contrast to the gold(III) compounds [Au(phen)Cl2]PF6 and [Au(bnpy)Cl2]. Additionally, we identify a potential role of Prdx6 in modulating the sensitivity of A-375 cells...

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Published in:Free radical biology & medicine 2024-11, Vol.224, p.346-351
Main Authors: Inague, Alex, Nakahata, Douglas H., Viviani, Lucas G., Alegria, Thiago G.P., Lima, Rodrigo S., Iijima, Thais S., Netto, Luís Eduardo S., Angeli, José Pedro F., Miyamoto, Sayuri, de Paiva, Raphael E.F.
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Language:English
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Summary:In this study, we demonstrate that ferroptosis is a component of the cell death mechanism induced by auranofin in HT-1080 cells, in contrast to the gold(III) compounds [Au(phen)Cl2]PF6 and [Au(bnpy)Cl2]. Additionally, we identify a potential role of Prdx6 in modulating the sensitivity of A-375 cells to auranofin treatment, whereas the gold(III) compounds evaluated here exhibit Prdx6-independent cytotoxicity. Finally, using mass spectrometry, we show that auranofin binds selectively to the catalytic Cys47 residue of Prdx6 in vitro under acidic conditions. No binding was observed with the C47S mutant or at neutral pH. [Display omitted] •Ferroptosis and Prdx6 role in protection were evaluated for three gold compounds.•The Au(I) compound auranofin induced ferroptosis in HT-1080 cells, while Au(III) compounds did not.•Knockout of Prdx6 in A-375 cells led to higher sensitivity, only in the case of auranofin treatment.•Auranofin binds to Prdx6 in vitro at Cys47, in acidic pH.
ISSN:0891-5849
1873-4596
1873-4596
DOI:10.1016/j.freeradbiomed.2024.08.042