Figure 2.

Potential cooperative targeting of the thioredoxin system by 1,25(OH)₂D₃ and auranofin. Induction of thioredoxin-interacting protein (TXNIP)/ vitamin D3-upregulated protein 1 (VDUP1) expression with 1,25(OH)₂D₃ and inhibition of thioredoxin reductase (TrxR) by auranofin and other gold complexes could synergistically inhibit the reductive capacity of the thioredoxin (Trx) system, subsequently increasing intracellular reactive oxygen species (ROS) levels, which activate apoptotic signaling. Besides influencing redox balance, 1,25(OH)₂D₃-mediated TXNIP induction may alter glucose homeostasis given the latter’s role in regulating intracellular glucose levels. Although this effect is independent of other players of the Trx system (hence not presented in figure), it could define novel anti-tumor roles of 1,25(OH)₂D₃.