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Saccharina japonica Extract Suppresses Stemness of Glioma Stem Cells by Degrading Epidermal Growth Factor Receptor/Epidermal Growth Factor Receptor Variant III

Journal of Medicinal Food 2018년 21권 5호 p.496 ~ 505
김소연, 김정엽, 신운섭, 이석준, 지성길, 이지윤, 박명진,
소속 상세정보
김소연 ( Kim So-Yeon ) - Korea Institute of Radiological and Medical Sciences Division of Radiation Cancer Research
김정엽 ( Kim Jeong-Yub ) - Korea Institute of Radiological and Medical Sciences Division of Radiation Cancer Research
신운섭 ( Shin Woon-Seob ) - Catholic Kwandong University College of Medicine Department of Microbiology
이석준 ( Lee Seok-Joon ) - Catholic Kwandong University College of Medicine Department of Pharmacology
지성길 ( Chi Sung-Gil ) - Korea University School of Life Sciences and Biotechnology
이지윤 ( Lee Ji-Yun ) - Korea University College of Medicine Department of Pathology
박명진 ( Park Myung-Jin ) - Korea Institute of Radiological and Medical Sciences Division of Radiation Cancer Research

Abstract


Cancer stem cells, a small subpopulation of cells with stem cell-like characteristics found within most solid tumors, are widely reported to be responsible for the malignancy of aggressive cancer cells, and targeting these cells presents a sound therapeutic strategy for reducing the risk of tumor relapse. In the present study, we examined the effects of an extract of Saccharina japonica (ESJ) on glioblastoma stem cells (GSCs). Saccharina japonica is a member of the Phaeophyceae (brown algae) family, which displays biological activities, including antitumor effects. ESJ inhibited the sphere-forming ability of GSCs in vitro as evidenced by neurosphere formation and limiting dilution assays. Treatment with ESJ partially induced apoptosis, reduced cell invasiveness, and sensitized GSCs to ionizing radiation. In addition, ESJ inhibited the maintenance of stemness in GSCs by suppressing the expression of epidermal growth factor receptor (EGFR)/EGFR variant III (EGFRvIII) and Notch intracellular domain. Intriguingly, the observed ESJ-induced suppression also appeared to induce the proteasomal degradation of EGFR/EGFRvIII. Our results indicate that ESJ could be considered a potent therapeutic adjuvant that targets GSCs.

키워드

EGFR; EGFRvIII; glioblastoma stem cells; Saccharina japonica; stemness

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