國家衛生研究院 NHRI:Item 3990099045/6129
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6129


    Title: Combination of arsenic trioxide and BCNU synergistically triggers redox-mediated autophagic cell death in human solid tumors
    Authors: Kuo, CC;Liu, TW;Chen, LT;Shiah, HS;Wu, CM;Cheng, YT;Pan, WY;Liu, JF;Chen, KL;Yang, YN;Chen, SN;Chang, JY
    Contributors: National Institute of Cancer Research
    Abstract: Arsenic trioxide (As2O3) is an effective treatment for relapsed or refractory acute promyelocytic leukemia (APL). After the discovery of As2O3 as a promising treatment for APL, several studies investigated the use of As2O3 as a single agent in the treatment of solid tumors; however, its therapeutic efficacy is limited. Thus, the systematic study of the combination of As2O3 with other clinically used chemotherapeutic drugs to improve its therapeutic efficacy in treating human solid tumors is merited. In this study, we demonstrate for the first time, using isobologram analysis, that As2O3 exhibits a synergistic interaction with N,N′-bis(2-chloroethyl)-N-nitrosourea (BCNU). The synergistic augmentation of the cytotoxicity of As2O3 with BCNU is in part through the autophagic cell death machinery in human solid tumor cells. As2O3 and BCNU in combination produce enhanced cytotoxicity via the depletion of reduced glutathione (GSH) and augmentation of reaction oxygen species (ROS) production. Further analysis indicated that the extension of GSH depletion by this combined regimen occurs through the inhibition of the catalytic activity of glutathione reductase. Blocking ROS production with antioxidants or ROS scavengers effectively inhibits cell death and autophagy formation, indicating that redox-mediated autophagic cell death involves the synergism of As2O3 with BCNU. Taken together, this is the first evidence that BCNU could help to extend the therapeutic spectrum of As2O3. These findings will be useful in designing future clinical trials of combination chemotherapy with As2O3 and BCNU, with the potential for broad use against a variety of solid tumors.
    Date: 2011-12-15
    Relation: Free Radical Biology and Medicine. 2011 Dec 15;51(12):2195-2209.
    Link to: http://dx.doi.org/10.1016/j.freeradbiomed.2011.09.023
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0891-5849&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000297960000009
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=81855176014
    Appears in Collections:[Jang-Yang Chang] Periodical Articles
    [Her-Shyong Shiah(1996-2012)] Periodical Articles
    [Li-Tzong Chen] Periodical Articles
    [Tsang-Wu Liu] Periodical Articles
    [Ching-Chuan Kuo] Periodical Articles

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