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

Author(s)

Inague, Alex ; Nakahata, Douglas H. ; Viviani, Lucas G. ; Alegria, Thiago G. P. ; Lima, Rodrigo S. ; Iijima, Thais S. ; Netto, Luis Eduardo S. ; Angeli, Jose Pedro F. ; Miyamoto, Sayuri ; de Paiva, Raphael E. F.

• Document type: Journal article
• Source: Free Radical Biology and Medicine; v. 224, p. 6-pg., 2024-09-04.

Abstract

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 2 ]PF 6 and [Au(bnpy)Cl2]. 2 ]. 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. (AU)

• FAPESP's process: 17/13804-1 - Mechanisms of detoxification and repair of oxidized biological membranes involving the action of the enzyme peroxiredoxin 6
• Grantee: Alex Inague
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 21/10514-8 - Identification and selection of inhibitors and/or activators of enzymes involved in the formation and detoxification of oxidized lipids
• Grantee: Lucas Gasparello Viviani
• Support Opportunities: Scholarships in Brazil - Post-Doctoral