title: Inhibition of Wnt/β-Catenin Pathway by Dehydrocostus Lactone and Costunolide in Colon Cancer Cells.
abstract: Abnormal activation of β-catenin has been reported in 90% in the sporadic and hereditary colorectal cancer. The suppression of abnormally activated β-catenin is one of the good strategies for chemoprevention and treatment of colorectal cancer. In this study, we have isolated two main compounds from root of Saussurea lappa, dehydrocostus lactone (DCL) and costunolide (CL), and investigated their anti-colorectal cancer activities. DCL and CL suppressed cyclin D1 and survivin through inhibiting nuclear translocation of β-catenin. They also suppressed the nuclear translocation of galectin-3 that is one of the coactivators of β-catenin in SW-480 colon cancer cells. Furthermore, DCL and CL suppressed proliferation and survival of SW-480 colon cancer cells through the induction of cell cycle arrest and cell death. Taken together, DCL and CL from root of S. lappa have anti-colorectal cancer activities through inhibiting Wnt/β-catenin pathway.
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 52 Hyochangwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea.
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Dong
authors.forename: Ah-Ram
authors.initials: AR
authors.lastname: Shim
authors.forename: Jin Seong
authors.initials: JS
authors.lastname: Hyeon
authors.forename: Hwa Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D001798:Blood Proteins; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000378:metabolism; D037502:Galectin 3 / Q000378:metabolism; D037161:Galectins; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D030441:Saussurea / Q000737:chemistry; D012717:Sesquiterpenes / Q000494:pharmacology*; D000077022:Survivin; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D001798:Blood Proteins; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; D037502:Galectin 3; D037161:Galectins; D051034:Inhibitor of Apoptosis Proteins; C428445:LGALS3 protein, human; D007783:Lactones; D012717:Sesquiterpenes; D000077022:Survivin; D051176:beta Catenin; D019938:Cyclin D1; C083030:dehydrocostus lactone; C002602:costunolide
keywords: colon cancer cell; costunolide; dehydrocostus lactone; β-catenin