Quercetin, a potent inhibitor against β-catenin/Tcf signaling in SW480 colon cancer cells
Section snippets
Materials and methods
Cell lines and reagents. SW480 and HEK293 cell lines were derived from Korean Cell Line Bank (KCLB, Korea). Quercetin was purchased from Acros. Stock solutions (50 mM) were made in DMSO. TOPflash was provided by Hans Clevers via Bart O Williams, and wild (pcDNA β-catenin) and mutant β-catenin gene (pcDNA S33Y) were provided by Eric R. Fearon.
Isolation of cellular and nuclear extracts. Cells were trypsinized and whole cell protein was obtained by lysing the cells on ice for 20 min in 700 μl lysis
Quercetin downregulates the β-catenin/Tcf signaling
To investigate whether quercetin modulates β-catenin/Tcf signaling, we used SW480 human colon cancer cells (Fig. 2A) and HEK293 cells transiently transfected with wild β-catenin gene (Fig. 2B). The transcriptional activity of β-catenin/Tcf is constitutively active in SW480 cell line (mutant APC, wild-type CTNNB1, and COX-2 negative). We used reporter gene constructs containing four copies of either an optimized (TOPflash) or mutant (FOPflash) Tcf-binding element. SW480 cells were cotransfected
Discussion
Flavonoids constitute one of the largest groups of naturally occurring phenols and are commonly present in plants as glycosides. These compounds possess a common phenylbenzopyrone structure (C6–C3–C6), and they are categorized according to the saturation level and opening of the central pyran ring, mainly into flavones, flavanols, isoflavones, flavonols, flavanones, and flavanonols [21], [22]. These dietary anti-oxidants are well known to exert significant anti-tumor effects and have been
Acknowledgments
We thank Dr. H. Clevers for the gift of TOPflash. We also thank Dr. Eric R. Fearon for the wild (pcDNA β-catenin) and mutant β-catenin gene (pcDNA S33Y). This research was supported by a grant (KRF 2001-015-DP0344) from the Korean Ministry of Science and Technology. Financial support in part from the Brain Korea 21 program is gratefully acknowledged.
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