Negative regulation of β-catenin/Tcf signaling by naringenin in AGS gastric cancer cell

Functional activation of β-catenin/Tcf signaling plays an important role in early events in carcinogenesis. We examined the effect of naringenin against β-catenin/Tcf signaling in gastric cancer cells. Reporter gene assay showed that naringenin inhibited β-catenin/Tcf signaling efficiently. In addition, the inhibition of β-catenin/Tcf signaling by naringenin in HEK293 cells transiently transfected with constitutively mutant β-catenin gene, whose product is not phosphorylated by GSK3β, indicates that its inhibitory mechanism was related to β-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunofluorescence, Western blot, and EMSA. As a result, our data revealed that the β-catenin distribution and the levels of nuclear β-catenin and Tcf-4 proteins were unchanged after naringenin treatment. Moreover, the binding activities of Tcf complexes to consensus DNA were not affected by naringenin. Taken together, these data suggest that naringenin inhibits β-catenin/Tcf signaling in gastric cancer with unknown mechanisms.