Thiosemicarbazones selectively oxidize peroxiredoxin-3 (Prx3) in cancer cells.
Decreased cell survival to thiosemicarbazones closely correlates with Prx3 oxidation.
Suppression of Prx3 or thioredoxin-2, which supports Prx3, enhances cytotoxicity.
Inhibitors of thioredoxin reductase markedly enhance triapine’s cytotoxicity.
Targeting Prx3 with thiosemicarbazone regimens is a promising anti-tumor approach.