Hydrogen peroxide negatively modulates Wnt signaling through downregulation of beta-catenin.

The Wnt signal transduction pathway plays an important role in organogenesis and carcinogenesis. In an effort to better understand the action of oxidative stress-induced cellular signaling, we investigate the effect of exogenous H2O2 on the Wnt signal pathway. H2O2 decreases the amount of nuclear beta-catenin and Tcf/Lef-dependent transcription. Overexpression of Dvl-1 abrogated H2O2-induced downregulation of beta-catenin. Pretreatment with LiCl or Wnt-3a conditioned medium completely inhibited H2O2-induced release of mitochondrial cytochrome c and DNA fragmentation. These results suggest that H2O2 negatively modulates the Wnt signal pathway through downregulation of beta-catenin.