Gomisins J and N, Dibenzocyclooctadiene Lignans from the Fruit of Schisandra chinensis, Inhibit the Wnt/β-catenin Signaling Pathway in HCT116 Cells
- Gomisins J and N, Dibenzocyclooctadiene Lignans from the Fruit of Schisandra chinensis, Inhibit the Wnt/β-catenin Signaling Pathway in HCT116 Cells
- 강경수; 이경미; 유지혜; 이희주; 김철영; 노주원
- Wnt/β-catenin; cancer chemoprevention; Gomisins; Schisandra chinensis; Dibenzocyclooctadiene lignan; Cyclin D1
- Issue Date
- The Wnt/β-catenin signaling pathway is a crucial pathway that contributes to human carcinogenesis including colorectal cancer, and inhibitors of the Wnt/β-catenin pathway may be good candidates as cancer chemopreventive agents. Many Wnt inhibitors derived from natural sources, such as flavonoids, terpenoids, and alkaloids have been reported. To date, the mechanism by which lignans inhibit the Wnt/β-catenin signaling pathway has been poorly understood. We show here, for the first time, that the lignans gomisin J and gomisin N inhibit the Wnt/β-catenin signaling pathway. Gomisins J and N are dibenzocyclooctadiene-type lignans isolated from the fruit of Schisandra chinensis, which has been consumed as a component of tea and wine in East Asia for many years. Gomisins J and N inhibited Wnt/β-catenin signaling by disrupting the interaction between β-catenin and its specific DNA sequences called TCF binding elements (TBE) rather than by altering the expression of the β-catenin protein. Gomisins J and N actually inhibited HCT116 cell proliferation through the induction of cell cycle arrest at G0/G1 phase. Gomisins J and N induced a decrease in the protein expression of Cyclin D1, a representative target gene of the Wnt/β-catenin signaling pathway that regulates the G1 phase of the cell cycle. Gomsins J and N also induced a decrease of the protein expression of Cdk2 and Cdk4, which are important cyclin-dependent kinases that regulate G1/S transition and G1 progression, respectively. Gomisin N induced apoptosis, but gomisin J did not induce apoptosis in HCT116 cells. Taken togerther, gomisins J and N, the novel Wnt/β-catenin inhibitors discovered in this study, may serve as potential neutraceuticals for the prevention or treatment of human colorectal cancers.
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