Figure 3.

Thioredoxin reductase (TrxR) as a novel target for cancer therapy. Gold compounds, nitrosoureas, arsenic trioxide, dinitrohalobenzenes, curcumin, flavonoids, quinones, and other cancer chemotherapeutics have been shown to be TrxR inhibitors. TrxR inhibition blocks thioredoxin (Trx)-mediated activity in various processes, such as defense against oxidative stress, DNA replication and repair, apoptosis inhibition, transcription control, and protein folding via different signaling pathways. Some inhibitors, such as 1-chloro-2,4-dinitrobenzene (DNCB) and curcumin, modify TrxR via the alkylation of Cys⁴⁹⁶ and redox-active Sec⁴⁹⁷ residues and induce nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, finally leading to reactive oxygen species (ROS) production.