國家衛生研究院 NHRI:Item 3990099045/2717
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2717


    Title: A novel bis-benzylidenecyclopentanone derivative, BPR0Y007, inducing a rapid caspase activation involving upregulation of Fas (CD95/APO-1) and wild-type p53 in human oral epidermoid carcinoma cells
    Authors: Juang, SH;Pan, WY;Kuo, CC;Liou, JP;Hung, YM;Chen, LT;Hsieh, HP;Chang, JY
    Contributors: National Institute of Cancer Research;Division of Biotechnology and Pharmaceutical Research
    Abstract: BPROY007, a bis-benzylidenecyclopentanone derivative (2,5-bis-(4-hydroxy-3-methoxybenzylidene) cyclopentanone), was identified in our laboratory as a novel antineoplastic agent with a broad spectrum of antitumor activity against many human cancer cells. A previous study showed that BPROY007 inhibited DNA topoisomerase I (Top 1) activity and prevented tubulin polymerization. Notably, no cross-resistance with BPROY007 was observed in camptothecin-, VP-16- or vincristine-resistant cell lines. In this study, we further investigated the cellular and molecular events underlying the antitumoral function of this compound in human oral epidermoid carcinoma KB cells, focusing on the early cytotoxic effect. Treatment of KB cells with BPROY007-induced G(2)/M phase arrest followed by sub-G, phase accumulation. Annexin-V-propidium iodide (PI) binding assay and DNA fragmentation assay further indicated that B PROY007-induced cell death proceeded through an apoptotic pathway as opposed to via necrosis. This compound produced a time-dependent activation of caspases-3 and -8, however, another caspase-3 initiator, caspase-9, was only marginally activated at later time point. We further demonstrated that the activation of the caspases cascade and nuclear fragmentation was not associated with inactivated Bcl-2 and perturbed mitochondrial membrane potential by BPROY007. The finding that BPROY007-induced apoptosis through a membrane-mediated mechanism was supported by up-regulated expression of Fas (CD95/APO-1), but not Fas-L. Furthermore, up-regulation of p53 and its affected gene, MDM2, in KB cells was found after BPROY007 exposure. Overall, our results demonstrated that the BPROY007 could induce an early cytotoxic apoptosis through a caspase-8-dependent but mitochondrial-caspase-9 independent pathway, and involving upregulation of p53. (C) 2004 Elsevier Inc. All rights reserved.
    Keywords: Pharmacology & Pharmacy
    Date: 2004-07-15
    Relation: Biochemical Pharmacology. 2004 Jul;68(2):293-303.
    Link to: http://dx.doi.org/10.1016/j.bcp.2004.03.036
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-2952&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000222308200010
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=2942573028
    Appears in Collections:[Jang-Yang Chang] Periodical Articles
    [Hsing-Pang Hsieh] Periodical Articles
    [Shin-Hun P. Juang(1997-2004)] Periodical Articles
    [Ching-Chuan Kuo] Periodical Articles
    [Li-Tzong Chen] Periodical Articles

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