Reactive oxygen species (ROS) are produced as normal products of cellular metabolism,
which are essential for numerous cell biological functions. Due to aberrant metabolism, oncogenic
signaling activation and mitochondrial dysfunction, cancer cells generate excessive ROS that cause
severe oxidative damage, finally leading to tumor cell death. Thioredoxin reductase (TrxR), as an
important ROS-scavenging enzyme, is overexpressed in various human tumors and plays an important
role in regulating intracellular redox homeostasis to protect cancer cells from cell death induced by
substantial ROS. Hence, TrxR has emerged as a promising target for anticancer agent development.
Currently, metallodrugs with anticancer activity, especially gold- and platinum-complexes, have an
enormous impact on clinical cancer chemotherapy. This review provides a comprehensive overview of
various metal complexes (gold, platinum, ruthenium, rhodium, iridium, iron, palladium, silver,
antimony, bismuth, tin) targeting mammalian TrxR and discusses their cytotoxicity in tumor cells.