Abstract
Activated β-catenin/T-cell factor (Tcf) signalling plays a role in human carcinogenesis. We identified the inhibitory effect of nordihydroguaiaretic acid (NDGA) against β-catenin/Tcf signalling in β-catenin activated cells. NDGA 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 NDGA. Immunoprecipitation analysis also showed that the binding of β-catenin to Tcf-4 was also disrupted by NDGA. Western blot analysis showed a decreased level of β-catenin in nucleus caused by NDGA. NDGA did not decrease phosphorylation of Akt and GSK3β. Taken together, these results suggest that the NDGA acts as a negative regulator of β-catenin/Tcf signalling and its inhibitory mechanism is related to the decreased binding of β-catenin/Tcf complexes to consensus DNA.
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