國家衛生研究院 NHRI:Item 3990099045/8647
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/8647


    Title: Elimination of cancer stem-like cells and potentiation of temozolomide sensitivity by honokiol in glioblastoma multiforme cells
    Authors: Lai, IC;Shih, PH;Yao, CJ;Yeh, CT;Wang-Peng, J;Lui, TN;Chuang, SE;Hu, TS;Lai, TY;Lai, GM
    Contributors: National Institute of Cancer Research
    Abstract: Glioblastoma multiforme (GBM) is the most common adult malignant glioma with poor prognosis due to the resistance to radiotherapy and chemotherapy, which might be critically involved in the repopulation of cancer stem cells (CSCs) after treatment. We had investigated the characteristics of cancer stem-like side population (SP) cells sorted from GBM cells, and studied the effect of Honokiol targeting on CSCs. GBM8401 SP cells possessed the stem cell markers, such as nestin, CD133 and Oct4, and the expressions of self-renewal related stemness genes, such as SMO, Notch3 and IHH (Indian Hedgehog). Honokiol inhibited the proliferation of both GBM8401 parental cells and SP cells in a dose-dependent manner, the IC50 were 5.3+/-0.72 and 11+/-1.1 muM, respectively. The proportions of SP in GBM8401 cells were diminished by Honokiol from 1.5+/-0.22% down to 0.3+/-0.02% and 0.2+/-0.01% at doses of 2.5 muM and 5 muM, respectively. The SP cells appeared to have higher expression of O6-methylguanine-DNA methyltransferase (MGMT) and be more resistant to Temozolomide (TMZ). The resistance to TMZ could be only slightly reversed by MGMT inhibitor O6-benzylguanine (O6-BG), but markedly further enhanced by Honokiol addition. Such significant enhancement was accompanied with the higher induction of apoptosis, greater down-regulation of Notch3 as well as its downstream Hes1 expressions in SP cells. Our data indicate that Honokiol might have clinical benefits for the GBM patients who are refractory to TMZ treatment.
    Date: 2015-03-12
    Relation: PLoS ONE. 2015 Mar 12;10(3):Article number e0114830.
    Link to: http://dx.doi.org/10.1371/journal.pone.0114830
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1932-6203&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000351276300001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84928923362
    Appears in Collections:[Gi-Ming Lai(2004-2008)] Periodical Articles
    [Shuang-En Chuang] Periodical Articles

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