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  • Title: Inhibition of beta-catenin/Tcf signaling by flavonoids.
    Author: Park S, Choi J.
    Journal: J Cell Biochem; 2010 Aug 15; 110(6):1376-85. PubMed ID: 20564233.
    Abstract:
    Functional activation of beta-catenin/T-cell factor (Tcf) signaling has been implicated in human carcinogenesis. We identified the inhibitory effect of various polyphenolic flavonoid compounds against beta-catenin/Tcf signaling in beta-catenin-activated cells. Genistein, kaempferol, isorhamnentin, and baicalein inhibited the transcriptional activity of beta-catenin/Tcf in HEK293 cells transiently transfected with a constitutively active mutant beta-catenin gene. To investigate the inhibitory mechanism, electrophoresis mobility shift assay, immunoprecipitation, and Western blot experiments were performed. The shift assay showed that the binding of Tcf complexes with its specific DNA-binding sites was suppressed by four kinds of flavonoids. Immunoprecipitation analysis also showed that the binding of beta-catenin to Tcf-4 was also disrupted by these flavonoids. Western blot analysis showed a decreased level of beta-catenin in nucleus caused by genistein. Genistein also decreased phosphorylation of Akt and GSK3 beta. Taken together, these results suggest that the polyphenolic flavonoids genistein, kaempferol, isorhamnentin, and baicalein are negative regulators of beta-catenin/Tcf signaling and their inhibitory mechanism is related to the decreased binding of beta-catenin/Tcf complexes to consensus DNA.
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