Thioredoxin reductase 1 deficiency enhances selenite toxicity in cancer cells via a thioredoxin-independent mechanism

• DOI: 10.1042/bj20120618
• Publication Date: 2012-05-18T08:11:27Z
• Authors: Ryuta Tobe; Min-Hyuk Yoo; Noelia Fradejas; Bradley A. Carlson; Soledad Calvo; Vadim N. Gladyshev; Dolph L. Hatfield
• Keywords: Glutathione reductase

Selenium is an essential trace element in mammals, but toxic at high levels. It best known for its cancer prevention activity, cells are more sensitive to selenite toxicity than normal cells. Since treatment leads oxidative stress, and the Trx (thioredoxin) system a major antioxidative system, we examined interplay between TR1 (Trx reductase 1) Trx1 deficiencies DT cells, malignant mouse cell line, corresponding parental NIH 3T3 TR1-deficient were far Trx1-deficient or control In contrast, this effect was not seen treated with hydrogen peroxide, suggesting that increased sensitivity of deficiency due stress caused by compound. Further analyses revealed only manifested strongly enhanced production secretion glutathione, which associated selenite. The results suggest new role independent reduction compensated glutathione system. also simultaneous inhibition can provide avenue therapy.