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## Abstract Functional activation of β‐catenin/T‐cell factor (Tcf) signaling has been implicated in human carcinogenesis. We identified the inhibitory effect of various polyphenolic flavonoid compounds against β‐catenin/Tcf signaling in β‐catenin‐activated cells. Genistein, kaempferol, isorhamnentin, and baicalein inhibited the transcriptional activity of β‐catenin/Tcf in HEK293 cells transiently transfected with a constitutively active mutant β‐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 β‐catenin to Tcf‐4 was also disrupted by these flavonoids. Western blot analysis showed a decreased level of β‐catenin in nucleus caused by genistein. Genistein also decreased phosphorylation of Akt and GSK3β. Taken together, these results suggest that the polyphenolic flavonoids genistein, kaempferol, isorhamnentin, and baicalein are negative regulators of β‐catenin/Tcf signaling and their

Author

Seyeon Park; Jaemin Choi

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0730-2312)

Published

2010

Language

EN