國家衛生研究院 NHRI:Item 3990099045/2700
English  |  正體中文  |  简体中文  |  Items with full text/Total items : 12145/12927 (94%)
Visitors : 851122      Online Users : 494
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
    •  Adv. Search
    Home ‧ Login ‧ Upload ‧ Help ‧ About ‧ Administer Goto mobile version


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2700


    Title: Mitochondria-mediated and p53-associated apoptosis induced in human cancer cells by a novel selenophene derivative, D-501036
    Authors: Shiah, HS;Lee, WS;Juang, SH;Hong, PC;Lung, CC;Chang, CJ;Chou, KM;Chang, FY
    Contributors: National Institute of Cancer Research
    Abstract: D-501036 [2,5-bis(5-hydroxymethyl-2-selenienyl)-3-hydroxymethyl-N-methylpyrrol], a novel selenophene derivative, is a highly potent cytotoxic agent with broad spectrum antitumor activity. The present study was undertaken to explore the mechanism(s) through which D501036 exerts its action mode on the cancer cell death. D-501036 was found to suppress the growth of KB and HepG(2) cells in an irreversible manner. The results of annexin-V assays and PARP cleavage studies were consistent with the D-501036-induced apoptosis. Findings provided a strong support for the induction of mitochondria-mediated apoptosis by this drug. The examination of two canonical pathways of initiation caspases, those for caspases -8 and -9, revealed that caspase-9 protein and the activities of caspases -9 and -3 were increased in a dose- and time-dependent manner. The concentrations of Fas/Fas-L and procaspase-8 and the activity of caspase-8 were not altered. Furthermore, the mitochondrial membrane potential permeability and the release of cytochrome c to the cytosol were both increased by D-501036. The concentrations of the pro-apoptotic protein Bax and translocation of Bax from the cytosol to the mitochondria were increased in response to D-501036, whereas the concentrations of the anti-apoptotic protein Bcl-2 were decreased. Two DNA damage-related pro-apoptotic proteins, Puma and Noxa, were upregulated in a dose- and time-dependent manner. These pro-apoptotic and anti-apoptotic proteins are downstream effectors of p53. Accordingly, the phosphorylated and total forms of p53 were induced and p53 was translocated from the cytosol to the mitochondria in response to D-501036 treatment. Collectively, we conclude that D-501036 induces cellular apoptosis through the p53-associated mitochondrial pathway. (c) 2006 Published by Elsevier Inc.
    Keywords: Pharmacology & Pharmacy
    Date: 2007-03-01
    Relation: Biochemical Pharmacology. 2007 Mar;73(5):610-619.
    Link to: http://dx.doi.org/10.1016/j.bcp.2006.10.019
    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:000244380100002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33846518865
    Appears in Collections:[Her-Shyong Shiah(1996-2012)] Periodical Articles
    [Jang-Yang Chang] Periodical Articles

    Files in This Item:

    File Description SizeFormat
    000244380100002.pdf816KbAdobe PDF1107View/Open


    All items in NHRI are protected by copyright, with all rights reserved.

    Related Items in TAIR

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback