title: Dibenzocyclooctadiene lignans, gomisins J and N inhibit the Wnt/β-catenin signaling pathway in HCT116 cells.
abstract: Here, we report that gomisin J and gomisin N, dibenzocyclooctadiene type lignans isolated from Schisandra chinensis, inhibit Wnt/β-catenin signaling in HCT116 cells. Gomisins J and N appear to inhibit Wnt/β-catenin signaling by disrupting the interaction between β-catenin and its specific target DNA sequences (TCF binding elements, TBE) rather than by altering the expression of the β-catenin protein. Gomisins J and N inhibit HCT116 cell proliferation by arresting the cell cycle at the G0/G1 phase. The G0/G1 phase arrest induced by gomisins J and N appears to be caused by a decrease in the expression of Cyclin D1, a representative target gene of the Wnt/β-catenin signaling pathway, as well as Cdk2, Cdk4, and E2F-1. Therefore, gomisins J and N, the novel Wnt/β-catenin inhibitors discovered in this study, may serve as potential agents for the prevention and treatment of human colorectal cancers.
authors.affiliation: Functional Food Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea.
authors.forename: Kyungsu
authors.initials: K
authors.lastname: Kang
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Lee
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Yoo
authors.forename: Hee Ju
authors.initials: HJ
authors.lastname: Lee
authors.forename: Chul Young
authors.initials: CY
authors.lastname: Kim
authors.forename: Chu Won
authors.initials: CW
authors.lastname: Nho
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D034242:Cyclooctanes / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000494:pharmacology*; D012045:Regulatory Sequences, Nucleic Acid; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D051820:TCF Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D034242:Cyclooctanes; D017705:Lignans; D011083:Polycyclic Compounds; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C510994:dibenzocyclooctadiene lignan; C015499:schizandrin B; D019938:Cyclin D1; C082091:gomisin J