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

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1 Citation (Scopus)


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.

Original languageEnglish
Article number13990
JournalScientific reports
Issue number1
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
This study was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science and ICT (NRF-2020M2D9A2092372); the government of Korea (MSIT) (NRF-2022R1A2B5B03001199); the Bio and Medical Technology Development Program of the National Research Foundation (NRF), funded by the Ministry of Science and ICT (NRF-2020M3E5E2037960); a “Team Science Award” of Yonsei University College of Medicine (6-2021-0192); and the Hanim Precision Medicine Center of Yonsei University Health System under Grant number (6-2021-0127) to S.G.K.

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

  • General


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