Emodin suppresses maintenance of stemness by augmenting proteosomal degradation of epidermal growth factor receptor/epidermal growth factor receptor variant III in glioma stem cells

Jeongyub Kim, Jong Seon Lee, Jieun Jung, Inhye Lim, Ji Yun Lee, Myung Jin Park

    Research output: Contribution to journalArticlepeer-review

    18 Citations (Scopus)

    Abstract

    There is a growing body of evidence that small subpopulations of cells with stem cell-like characteristics within most solid tumors are responsible for the malignancy of aggressive cancer cells and that targeting these cells might be a good therapeutic strategy to reduce the risk of tumor relapse after therapy. Here, we examined the effects of emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active component of the root and rhizome of Rheum palmatum that has several biological activities, including antitumor effects, on primary cultured glioma stem cells (GSCs). Emodin inhibited the self-renewal activity of GSCs in vitro as evidenced by neurosphere formation, limiting dilution, and soft agar clonogenic assays. Emodin inhibited the maintenance of stemness by suppressing the expression of Notch intracellular domain, nonphosphorylated β-catenin, and phosphorylated STAT3 proteins. In addition, treatment with emodin partially induced apoptosis, reduced cell invasiveness, and sensitized GSCs to ionizing radiation. Intriguingly, emodin induced proteosomal degradation of epidermal growth factor receptor (EGFR)/EGFR variant III (EGFRvIII) by interfering with the association of EGFR/EGFRvIII with heat shock protein 90, resulting in the suppression of stemness pathways. Based on these data, we propose that emodin could be considered as a potent therapeutic adjuvant that targets GSCs.

    Original languageEnglish
    Pages (from-to)284-295
    Number of pages12
    JournalStem cells and development
    Volume24
    Issue number3
    DOIs
    Publication statusPublished - 2015 Feb 1

    ASJC Scopus subject areas

    • Hematology
    • Developmental Biology
    • Cell Biology

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