Treatment of human cancer cells with selenite or tellurite in combination with auranofin enhances cell death due to redox shift.

Abstract

Selenium is an essential trace element incorporated as selenocysteine in 25 human selenoproteins. Among them are thioredoxin reductases (TrxR) and glutathione peroxidases, all central proteins in the regulation of the cellular thiol redox state. In this paper the effects of selenite and tellurite treatment in human cancer cells are reported and compared. Our results show that both selenite and tellurite, at relatively low concentrations, are able to increase the expression of mitochondrial and cytosolic TrxR in cisplatin-sensitive (2008) and -resistant (C13*) phenotypes. We further investigated the cellular effects induced by selenite or tellurite in combination with the specific TrxR inhibitor auranofin. Selenite pretreatment induced a dramatic increase in auranofin cytotoxicity in both resistant and sensitive cells. Investigation of TrxR activity and expression levels as well as the cellular redox state demonstrated the involvement of TrxR inhibition and redox changes in selenite and auranofin combined action.

• Authors: Maria Pia Rigobello, Valentina Gandin, Alessandra Folda, Anna-Klara Rundlöf, Aristi P Fernandes, Alberto Bindoli, Cristina Marzano, Mikael Björnstedt
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 47 Issue 6 Pg. 710-21 (Sep 15 2009) ISSN: 1873-4596 [Electronic] United States
• PMID: 19486940 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Auranofin
• Thioredoxin-Disulfide Reductase
• Sodium Selenite
• tellurous acid
• Tellurium
• Cisplatin

Topics

• Adenocarcinoma (drug therapy, genetics, metabolism, secondary)
• Auranofin (pharmacology)
• Cell Death (drug effects)
• Cell Line, Tumor
• Cisplatin (therapeutic use)
• Drug Resistance, Neoplasm
• Enzyme Inhibitors (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (drug therapy, genetics, metabolism, pathology)
• Ovarian Neoplasms (drug therapy, genetics, metabolism, secondary)
• Sodium Selenite (pharmacology, therapeutic use)
• Tellurium (pharmacology, therapeutic use)
• Thioredoxin-Disulfide Reductase (genetics, metabolism)