Selenocytotoxicity and redoxsystems : The effect of selenocompounds on redoxsystems in tumor cells

Abstract:   The Thioredoxin (Trx) and Glutaredoxin (Grx) system are two major antioxidant redoxsystems in the cells that prevent and respond to oxidative stress, which is a well known factor in aging and causing several diseases, like neurodegenerative disorders, diabetes and cancer. Oxidative stress also can be described as an imbalance between production of reactive oxygen species (ROS) and the cellular protection. Thioredoxin Reductase (TrxR), a selenoproteine located both in the cytosol and the mitochondria, functioning as an electron donor for Trx, and also its mithochondrial form (TrxR2) it can be an electron donor for Grx2.   Lately, several studies has been showing Selenite, a highly oxidized form of selenium, a well known essential tracemineral and antioxidant,  to be a potential therapeutic drug in cancer treatment by inhibiting tumor growth and induce apoptosis in cytostatic drug-resistant malign cell-lines. Gold, and gold-containing drugs have a long history in medicine, and has been validated as potent TrxR inhibitors. In this study we have combined Selenite and a Goldcompound in treatment of Grx2-overexpressing HeLa cell-lines, and investigated the inhibiting effect on the Thioredoxin and Glutaredoxin system, and also how Grx2 would function without its electron donor, TrxR2. By using a quantitative polymerase chain reaction and for this, we have successfully optimized a TrxR2-primer, measured and compared the expression of mRNA levels of TrxR1, TrxR2, Grx2 and Grx2tot.We have also investigated the enzyme kinetics of Grx1 with selenocysteine, selenodiglutathione and selenomethylselenocystine, to see/ and found that  they could be a substrate for Grx1.