Quercetin, a potent inhibitor against beta-catenin/Tcf signaling in SW480 colon cancer cells

Abstract

Dysregulation of Wnt/beta-catenin pathway plays a central role in early events in colorectal carcinogenesis. We examined the effect of quercetin, a famous anti-tumor agent, against beta-catenin/Tcf signaling in SW480 cells. Quercetin inhibited the transcriptional activity of beta-catenin/Tcf in SW480 and also in HEK293 cells transiently transfected with constitutively active mutant beta-catenin gene, whose product is not induced to be degraded by APC-Axin-GSK3beta complex, so we concluded that its inhibitory mechanism was related to beta-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed EMSA showing that binding of the Tcf complexes to its specific DNA-binding sites was strongly suppressed by quercetin. Immunoprecipitation analysis also showed that the binding of beta-catenin to Tcf-4 was also disrupted by quercetin. Western blot analysis proved these decreased bindings resulted from decreased level of beta-catenin and Tcf-4 product in nucleus caused by quercetin. Together, we suggest that quercetin is an excellent inhibitor of beta-catenin/Tcf signaling in SW480 cell lines, and the reduced beta-catenin/Tcf transcriptional activity is due to the decreased nuclear beta-catenin and Tcf-4 proteins.