title: A Bacterial Metabolite, Compound K, Induces Programmed Necrosis in MCF-7 Cells via GSK3β.
abstract: Ginsenosides, the major active component of ginseng, are traditionally used to treat various diseases, including cancer, inflammation, and obesity. Among these, compound K (CK), an intestinal bacterial metabolite of the ginsenosides Rb1, Rb2, and Rc from Bacteroides JY-6, is reported to inhibit cancer cell growth by inducing cell-cycle arrest or cell death, including apoptosis and necrosis. However, the precise effect of CK on breast cancer cells remains unclear. MCF-7 cells were treated with CK (0-70 micrometer) for 24 or 48 h. Cell proliferation and death were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, respectively. Changes in downstream signaling molecules involved in cell death, including glycogen synthase kinase 3β (GSK3β), GSK3β, β-catenin, and cyclin D1, were analyzed by western blot assay. To block GSK3β signaling, MCF-7 cells were pretreated with GSK3β inhibitors 1 h prior to CK treatment. Cell death and the expression of β-catenin and cyclin D1 were then examined. CK dose- and time-dependently inhibited MCF-7 cell proliferation. Interestingly, CK induced programmed necrosis, but not apoptosis, via the GSK3β signaling pathway in MCF-7 cells. CK inhibited GSK3β phosphorylation, thereby suppressing the expression of β-catenin and cyclin D1. Our results suggest that CK induces programmed necrosis in MCF-7 breast cancer cells via the GSK3β signaling pathway.
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Chae Won
authors.initials: CW
authors.lastname: Kwak
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Son
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.|Biomodulation Major and Center for Food Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Min Jeong
authors.initials: MJ
authors.lastname: Gu
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Girak
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Lee
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Yoon Chul
authors.initials: YC
authors.lastname: Kye
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Han Wool
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Ki-Duk
authors.initials: KD
authors.lastname: Song
authors.affiliation: Division of Zoonoses, Center for Immunology and Pathology, Korea National Institute of Health, Osong 363-951, Republic of Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Chu
authors.affiliation: Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Gangwon-do 232-916, Republic of Korea.
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Park
authors.affiliation: Department of Animal Biotechnology, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Hak-Kyo
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Korean Ginseng Center for Most Valuable Product & Ginseng Genetic Resource Bank, Kyung Hee University, Youngin 446-701, Republic of Korea.
authors.forename: Deok-Chun
authors.initials: DC
authors.lastname: Yang
authors.affiliation: Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sprent
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.|Biomodulation Major and Center for Food Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea.|Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Gangwon-do 232-916, Republic of Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
mesh_terms: D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005562:Formazans / Q000032:analysis; D036145:Ginsenosides / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D061986:MCF-7 Cells; D013194:Staining and Labeling; D013778:Tetrazolium Salts / Q000032:analysis
chemical_list: D005562:Formazans; D036145:Ginsenosides; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D013778:Tetrazolium Salts; C079782:MTT formazan; C112772:ginsenoside compound K; C000605506:GSK3B protein, human
keywords: GSK3β; MCF-7; breast cancer cells; compound K; ginsenoside; programmed necrosis