國家衛生研究院 NHRI:Item 3990099045/10557
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10557


    Title: JNK/AP-1 activation contributes to tetrandrine resistance in T-cell acute lymphoblastic leukaemia
    Authors: Liou, JT;Lin, CS;Liao, YC;Ho, LJ;Yang, SP;Lai, JH
    Contributors: Institute of Cellular and Systems Medicine
    Abstract: T-cell acute lymphoblastic leukaemia (T-ALL) is a challenging malignancy with a high relapse rate attributed to drug resistance. Tetrandrine (TET), a bisbenzylisoquinoline alkaloid extracted from a Chinese herb, is a potential anti-cancer and anti-leukaemic drug. In this study we investigated the mechanisms of TET resistance in T-ALL cells in vitro. Among the four T-ALL cell lines tested, Jurkat and CEM cells exhibited the lowest and highest resistance to TET with IC50 values at 24 h of 4.31+/-0.12 and 16.53+/-3.32 mumol/L, respectively. When treated with TET, the activity of transcription factor activator protein 1 (AP-1) was significantly decreased in Jurkat cells but nearly constant in CEM cells. To avoid cell-specific variation in drug resistance and transcription factor activities, we established a TET-R Jurkat subclone with the estimated IC50 value of 10.90+/-.92 mumol/L by exposing the cells to increasing concentrations of TET. Interestingly, when treated with TET, TET-R Jurkat cells exhibited enhanced AP-1 and NF-kappaB activity, along with upregulation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways, whereas the expression of P-gp was not altered. Selective inhibition of JNK but not ERK suppressed AP-1 activity and TET resistance in TET-R Jurkat cells and in CEM cells. These results demonstrate that Jurkat cells acquire TET resistance through activation of the JNK/AP-1 pathway but not through P-gp expression. The JNK/AP-1 pathway may be a potential therapeutic target in relapsed T-ALL.
    Date: 2017-08
    Relation: Acta Pharmacologica Sinica. 2017 Aug;38(8):1171-1183.
    Link to: http://dx.doi.org/10.1038/aps.2017.26
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1671-4083&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000406872200008
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85026665175
    Appears in Collections:[Ling-Jun Ho] Periodical Articles

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