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Inhibition of β‐catenin/Tcf signaling by flavonoids
Author(s) -
Park Seyeon,
Choi Jaemin
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22654
Subject(s) - genistein , immunoprecipitation , kaempferol , catenin , western blot , microbiology and biotechnology , phosphorylation , transfection , chromatin immunoprecipitation , chemistry , baicalein , signal transduction , electrophoretic mobility shift assay , biology , biochemistry , transcription factor , flavonoid , wnt signaling pathway , gene expression , gene , pharmacology , genetics , promoter , antioxidant
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 inhibitory mechanism is related to the decreased binding of β‐catenin/Tcf complexes to consensus DNA. J. Cell. Biochem. 110: 1376–1385, 2010. © 2010 Wiley‐Liss, Inc.