The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH (Nicotinamide adenine dinucleotide compounds were found to induce antiproliferative effects towards several human cancer cells some of which endowed with cisplatin or multidrug resistance. In addition, they were able to activate caspase-3 and induce apoptosis observed as nucleosome formation and sub-G1 cell accumulation. The complexes with thiocyanate and xanthate ligands were particularly effective in inhibiting thioredoxin reductase and inducing apoptosis.Pharmacodynamic studies in human ovarian cancer cells allowed for the correlatation of intracellular drug accumulation with TrxR inhibition that leads to the induction of apoptosis via the mitochondrial pathway.