Impact of Quercetin and EGCG on Key Elements of the Wnt Pathway in Human Colon Carcinoma Cells

The flavonoids quercetin (QUE) and (−)-epigallocatechin-3-gallate (EGCG) are discussed as potential chemopreventive food constituents. Both compounds have been shown to affect a spectrum of different cellular signaling pathways. Glycogen synthase kinase-3β (GSK3β) is one of the key elements of the Wnt pathway, governing β-catenin homeostasis. The inhibition of GSK3 kinase activity might lead to the onset of β-catenin/TCF/LEF-mediated gene transcription, representing a potentially mitogenic stimulus. The aim of the study was to elucidate whether QUE and EGCG possibly mediate undesired proliferative stimuli in human colon carcinoma cells by interference with the Wnt pathway. In HT29 cells QUE did not inhibit the activity of GSK3α and -β, measured as phosphorylation at Ser21 and Ser9, respectively. In accordance, QUE did not substantially affect β-catenin homeostasis. In a reporter gene assay QUE was found to act as a weak inductor of T-cell factor/lymphoid enhancer factor (TCF/LEF) mediated luciferase expression, which was, however, not associated with a stimulation of cell growth. Treatment of HT29 cells with EGCG led to a potent inhibition of GSK3α and -β activity. Subsequently, the amount of phosphorylated β-catenin was diminished in a concentration-dependent manner. Concomitantly, the overall amount of β-catenin was decreased to a similar extent, which might result from a downregulation of β-catenin neogenesis, indicated by reduced levels of β-catenin mRNA. In accordance, no induction of TCF/LEF-mediated luciferase expression was observed. In conclusion, the results allow the assumption that QUE and EGCG do not mediate proliferative stimuli in HT29 cells by interference with key elements of the Wnt pathway. Keywords: Quercetin; (−)-epigallocatechin-3-gallate; glycogen synthase kinase; β-catenin; Wnt pathway