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- Title
The inhibitory mechanism of curcumin and its derivative against β-catenin/Tcf signaling
- Authors
Park, Chi Hoon; Hahm, Eun Ryeong; Park, Seyeon; Kim, Hyun-Kyung; Yang, Chul Hak
- Abstract
Abstract: We investigated the inhibitory mechanism of curcumin and its derivative (CHC007) against β-catenin/T-cell factor (Tcf) signaling in various cancer cell lines. Curcumin is known to inhibit β-catenin/Tcf transcriptional activity in HCT116 cells but not in SW620 cells. To clarify the inhibitory effect of curcumin against β-catenin/Tcf signaling, we tested several cancer cell lines. In addition, in order to verify the inhibitory mechanism, we performed reporter gene assay, Western blot, immunoprecipitation, and electrophoretic mobility shift assay. Since inhibitors downregulated the transcriptional activity of β-catenin/Tcf in HEK293 cells transiently transfected with S33Y mutant β-catenin gene, whose product is not induced to be degraded by adenomatous polyposis coli–Axin–glycogen synthase kinase 3β complex, we concluded that the inhibitory mechanism was related to β-catenin itself or downstream components. Western blot analysis suggested that no change in the amount of cytosolic and membranous β-catenin in a cell occurred; however, nuclear β-catenin and Tcf-4 proteins were markedly reduced by inhibitors and this lead to the diminished association of β-catenin with Tcf-4 and to the reduced binding to the consensus DNA. In the present study, we demonstrate that curcumin and its derivative are excellent inhibitors of β-catenin/Tcf signaling in all tested cancer cell lines and the reduced β-catenin/Tcf transcriptional activity is due to the decreased nuclear β-catenin and Tcf-4.
- Subjects
GLUCANS; CANCER cells; CELL culture; CELL lines
- Publication
FEBS Letters, 2005, Vol 579, Issue 13, p2965
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2005.04.013