國家衛生研究院 NHRI:Item 3990099045/3129
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3129


    Title: Induction of apoptosis by DC-81-indole conjugate agent through NF-kappa B and JNK/AP-1 pathway
    Authors: Hu, WP;Tsai, FY;Yu, HS;Sung, PJ;Chang, LS;Wang, JJ
    Contributors: Division of Environmental Health and Occupational Medicine
    Abstract: DC-81, an antitumor antibiotic produced by Streptomyces species, belongs to the pyrrolo[2,1-c] [ 1,4]benzodiazepine (PBD) family, which are potent inhibitors of nucleic acid synthesis. We previously reported an efficient synthesis of PBD hybrids linked with indole carboxylates. Recently, we have also shown that a PBD hybrid (IN6CPBD) agent can activate the apoptotic pathway mediated by mitochondria. In this study, we will examine the transcription factors nuclear factor-kappa B (NF-kappa B) and activator protein- 1 (AP-1) that functionally regulate cell proliferation, transformation, and apoptosis. To investigate the IN6CPBD-induced alterations in NF-kappa B and AP-1 activity that involve cell cycle regulation, we exposed human melanoma A375 cells to different concentrations of IN6CPBD. Our data revealed that treatment of A375 cells with IN6CPBD resulted in a marked loss of cells from the G2/M phase of the cell cycle and an increase in Ca2+ and cAMP and promoted phosphorylation of Jun N-terminal kinase (JNK) expression. By using the luciferase reporter assay, the NF-kappa B activities were decreased; however, AP-1 activity was further enhanced after A375 cells were treated with graded concentrations of IN6CPBD. Blockade of NF-kappa B or JNK activity further enhanced caspase-3 substrate PARP cleavage and subsequent apoptotic cell death.
    Keywords: Chemistry, Medicinal;Chemistry, Multidisciplinary;Toxicology
    Date: 2008-07
    Relation: Chemical Research in Toxicology. 2008 Jul;21(7):1330-1336.
    Link to: http://dx.doi.org/10.1021/tx700394h
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0893-228X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000257860700007
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=49049111105
    Appears in Collections:[Others] Periodical Articles

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