Unknown

Thiophosphate (SPO(3)) was recently shown to promote cysteine insertion at Sec (selenocysteine)-encoding UGA codons during selenoprotein synthesis. The irreversible targeting by cDDP [cis-diamminedichloroplatinum(II) or cisplatin] of the Sec residue in TrxR1 (thioredoxin reductase 1) contributes to cDDP cytotoxicity. This effect could possibly be attenuated in cells expressing less reactive Sec-to-cysteine-substituted TrxR1 variants, or pronounced in cells with higher levels of Sec-containing TrxR1. To test this, there were supplemented cells with either SPO(3) or selenium and subsequently determined total as well as specific activities of cellular TrxR1, together with extent of drug-induced cell death. It was found that cDDP became less cytotoxic after incubation of A549 or HCT116 cells with lower SPO(3) concentrations (100-300 μM), whereas higher SPO(3) (>300 μM) had pronounced direct cytotoxicity. NIH 3T3 cells showed low basal TrxR1 activity and high susceptibility to SPO(3) cytotoxicity, or to glutathione depletion.