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Increased sodium selenite cytotoxicity in thioredoxin reductase 1 knockdown cancer cells
Author(s) -
Tobe Ryuta,
Yoo MinHyuk,
FradejasVillar Noelia,
Carlson Bradley A,
Calvo Soledad,
Gladyshev Vadim N,
Hatfield Dolph L
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.110.6
Subject(s) - thioredoxin reductase , cytotoxicity , glutathione , thioredoxin , selenium , chemistry , gene knockdown , buthionine sulfoximine , glutathione reductase , cancer cell , oxidative stress , cell culture , cytotoxic t cell , biochemistry , cancer research , microbiology and biotechnology , enzyme , biology , glutathione peroxidase , cancer , apoptosis , in vitro , organic chemistry , genetics
Selenite has been shown to possess tumor‐specific cytotoxic effects possibly due to its role in generating oxidative stress at higher concentrations. The selenium‐containing protein thioredoxin reductase 1 (TR1) is over‐expressed in a variety of cancers and cancer cell lines. One of the major functions of TR1 is its role in reducing and maintaining Trx in the reduced state. TR1 has also been shown to reduce selenite. In this study, we examined the role of TR1 in selenite cytotoxicity by examining TR1 and Trx1 knockdown cancer cells. Cells were treated with either selenite or H 2 O 2 to investigate their sensitivity to possible stress induced by these components. TR1 deficient cells were remarkably more sensitive to selenite than the corresponding control cells. Interestingly, Trx1 deficient cells displayed a different sensitivity pattern to selenite and H 2 O 2 than TR1 deficient cells. Only TR1 deficient cells showed a dramatic increase in the levels of glutathione (GSH) metabolic enzymes following selenite exposure and a higher sensitivity to L‐buthionine‐sulfoximine, an inhibitor of GSH synthesis. These observations provide further evidence that TR1 plays an important role in selenite cytotoxicity and suggest a compensatory response by the glutathione system in its absence. This research was supported by the Intramural Research Program of the NIH, NCI, CCR.