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A Bacterial Metabolite, Compound K, Induces Programmed Necrosis in MCF-7 Cells via GSK3beta


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 3beta (GSK3beta), GSK3beta, beta-catenin, and cyclin D1, were analyzed by western blot assay. To block GSK3beta signaling, MCF-7 cells were pretreated with GSK3beta inhibitors 1 h prior to CK treatment. Cell death and the expression of beta-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 GSK3beta signaling pathway in MCF-7 cells. CK inhibited GSK3beta phosphorylation, thereby suppressing the expression of beta-catenin and cyclin D1. Our results suggest that CK induces programmed necrosis in MCF-7 breast cancer cells via the GSK3beta signaling pathway.

Type Journal
ISBN 1738-8872 (Electronic) 1017-7825 (Linking)
Authors Kwak, C. W. ; Son, Y. M. ; Gu, M. J. ; Kim, G. ; Lee, I. K. ; Kye, Y. C. ; Kim, H. W. ; Song, K. D. ; Chu, H. ; Park, B. C. ; Lee, H. K. ; Yang, D. C. ; Sprent, J. ; Yun, C. H.;
Responsible Garvan Author Prof Jonathan Sprent
Published Date 2015-01-01
Published Volume 25
Published Issue 7
Published Pages 1170-6
Status Published in-print
URL link to publisher's version
OpenAccess link to author's accepted manuscript version