Treatment of human cancer cells with selenite or tellurite in combination with auranofin enhances cell death due to redox shift.
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.
Rigobello
Maria Pia
MP
Dipartimento di Chimica Biologica, Università di Padova, 35121 Padova, Italy.
Gandin
Valentina
V
Folda
Alessandra
A
Rundlöf
Anna-Klara
AK
Fernandes
Aristi P
AP
Bindoli
Alberto
A
Marzano
Cristina
C
Björnstedt
Mikael
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D001310:Auranofin / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D018038:Sodium Selenite / Q000494:pharmacology* / Q000627:therapeutic use; D013691:Tellurium / Q000494:pharmacology* / Q000627:therapeutic use; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D001310:Auranofin; D013880:Thioredoxin-Disulfide Reductase; D018038:Sodium Selenite; C026660:tellurous acid; D013691:Tellurium; D002945:Cisplatin