The effects of lithium and myo-inositol on levels and localization of β-catenin and Myc in HeLa cells

Lithium is a mood stabilizer used in the treatment of bipolar disorder and is known to have potent teratogenic effects. Therapeutically relevant targets of lithium include the constitutively active kinase glycogen synthase kinase-3 (GSK-3), an effector in the Wnt/β-catenin intracellular signaling pathway, and inositol monophosphatase (IMPase), an effector in the inositol triphosphate (IP3) signaling pathway; both enzymes are inhibited by lithium treatment. Inhibition of GSK-3 leads to an increase in the nuclear activity of the transcription factor β-catenin, whereas inhibition of IMPase results in the loss of an effector of IP3 signaling, myo-inositol. myo-inositol has been shown to rescue the effects of knocking out GSK-3 in embryonic development, though the mechanisms surrounding this rescue have not yet been characterized. Here it i show that myo-inositol does not prevent β-catenin from being translocated into the nucleus in HeLa cells. However, myo-inositol does lead to a significant decrease in the levels of Myc, a target of β-catenin, in the cells. Thus, I conclude that antagonism of β-catenin-mediated signaling by myo-inositol may be mediated in a manner independent of the nuclear translocation of β-catenin.