國家衛生研究院 NHRI:Item 3990099045/2677
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2677


    Title: Inhibition of invasion and angiogenesis by zinc-chelating agent disulfiram
    Authors: Shiah, SG;Kao, YR;Wu, FYH;Wu, CW
    Contributors: National Institute of Cancer Research
    Abstract: Cell invasion and angiogenesis are crucial processes in cancer metastasis that require extracellular matrix (ECM) degradation. Proteolytic degradation of the ECM components is a central event of invasion and angiogenesis processes. During these processes, matrix metalloproteinases (MMPs) seem to be primarily responsible for much of the ECM degradation. Disulfiram is frequently used in the treatment of alcoholism and has been reported to possess antiretroviral activity and can eject intrinsic zinc out of human immunodeficiency virus (HIV) nucleocapsid protein. In this report, we show that disulfiram inhibited invasion and angiogenesis in both tumor and endothelial cells at nontoxic concentrations. The H-3-labeled type IV collagen degradation assay suggested that disulfiram has type IV collagenase inhibitory activity, and this inhibition was responsible for blocking invasion and angiogenesis through cell-mediated and non-cell-mediated pathways. However, the mechanisms underlying cell-mediated signal pathways are not fully characterized. Our data demonstrate that the non-cell-mediated pathway is dominant. Thus, disulfiram could directly interact with MMP-2 and MMP-9 and inhibit their proteolytic activity through a zinc-chelating mechanism. Addition of zinc could reverse the inhibition of invasiveness and collagenase inhibition through disulfiram treatment. This finding implies that MMP-2 and MMP-9 may be the inhibitory targets for a potential disulfiram treatment. These observations raise the possibility clinical therapeutic applications for disulfiram used as a potential inhibitor of metastatic cell invasion and angiogenesis.
    Keywords: Pharmacology & Pharmacy
    Date: 2003-11
    Relation: Molecular Pharmacology. 2003 Nov;64(5):1076-1084.
    Link to: http://dx.doi.org/10.1124/mol.64.5.1076
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0026-895X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000186076300009
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0142148099
    Appears in Collections:[Cheng-Wen Wu(1996-2008)] Periodical Articles
    [Shine-Gwo Shiah] Periodical Articles

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