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A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1

 Jin-Kyoung Shim  ;  Seung Hoon Lim  ;  Ji Hye Jeong  ;  Ran Joo Choi  ;  Yoojung Oh  ;  Junseong Park  ;  Sunghee Choi  ;  Junpyo Hong  ;  Seo Jin Kim  ;  Ju Hyung Moon  ;  Eui Hyun Kim  ;  Wan-Yee Teo  ;  Bong Jin Park  ;  Jong Hee Chang  ;  Jae-Ha Ryu  ;  Seok-Gu Kang 
 SCIENTIFIC REPORTS, Vol.12(1) : 13990, 2022-08 
Journal Title
Issue Date
Alnus* ; Animals ; Carcinogenesis / genetics ; Cell Line, Tumor ; Cell Proliferation ; Forkhead Box Protein M1 / genetics ; Forkhead Box Protein M1 / metabolism ; Gene Expression Regulation, Neoplastic ; Glioblastoma* / metabolism ; Humans ; Lignans* / pharmacology ; Lignans* / therapeutic use ; Mice ; beta Catenin / metabolism
Forkhead Box M1 (FOXM1) is known to regulate cell proliferation, apoptosis and tumorigenesis. The lignan, (-)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. The present study hypothesized that DFS can have anti-cancer effects against glioblastoma (GBM) tumorspheres (TSs). Immunoprecipitation and luciferase reporter assays were performed to evaluate the ability of DFS to suppress nuclear translocation of β-catenin through β-catenin/FOXM1 binding. DFS-pretreated GBM TSs were evaluated to assess the ability of DFS to inhibit GBM TSs and their transcriptional profiles. The in vivo efficacy was examined in orthotopic xenograft models of GBM. Expression of FOXM1 was higher in GBM than in normal tissues. DFS-induced FOXM1 protein degradation blocked β-catenin translocation into the nucleus and consequently suppressed downstream target genes of FOXM1 pathways. DFS inhibited cell viability and ATP levels, while increasing apoptosis, and it reduced tumorsphere formation and the invasiveness of GBM TSs. And DFS reduced the activities of transcription factors related to tumorigenesis, stemness, and invasiveness. DFS significantly inhibited tumor growth and prolonged the survival rate of mice in orthotopic xenograft models of GBM. It suggests that DFS inhibits the proliferation of GBM TSs by suppressing FOXM1. DFS may be a potential therapeutic agent to treat GBM.
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Kim, Eui Hyun(김의현) ORCID logo https://orcid.org/0000-0002-2523-7122
Moon, Ju Hyung(문주형)
Park, Junseong(박준성)
Oh, Yoojung(오유정)
Chang, Jong Hee(장종희) ORCID logo https://orcid.org/0000-0003-1509-9800
Choi, Ran Joo(최란주)
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