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    Please use this identifier to cite or link to this item: http://ir.meiho.edu.tw/ir/handle/987654321/1931


    Title: Induction of Apoptosis by 11-Dehydrosinulariolide via Mitochondrial Dysregulation and ER Stress Pathways in Human Melanoma Cells
    Authors: Tzu-Rong Su;Feng-Jen Tsai;Jen-Jie Lin;Han Hsiang Huang;Chien-Chih Chiu
    Contributors: 健康暨護理學院
    Keywords: melanoma;11-dehydrosinulariolide;mitochondrial dysregulation;ER stress
    Date: 2012
    Issue Date: 2012-11-06T08:32:34Z (UTC)
    Abstract: In this study the isolated compound 11-dehydrosinulariolide from soft coral
    Sinularia leptoclados possessed anti-proliferative, anti-migratory and apoptosis-inducing
    activities against A2058 melanoma cells. Anti-tumor effects of 11-dehydrosinulariolide
    were determined by MTT assay, cell migration assay and flow cytometry. Growth
    and migration of melanoma cells were dose-dependently inhibited by 2–8 μg/mL
    11-dehydrosinulariolide. Flow cytometric data indicated that 11-dehydrosinulariolide
    induces both early and late apoptosis in melanoma cells. It was found that the apoptosis
    induced by 11-dehydrosinulariolide is relevant to mitochondrial-mediated apoptosis via
    caspase-dependent pathways, elucidated by loss of mitochondrial membrane potential (ΔΨm),release of cytochrome C, activation of caspase-3/-9 and Bax as well as suppression of
    Bcl-2/Bcl-xL. The cleavage of PARP-1 suggested partial involvement of caspase-independent
    pathways. Immunoblotting data displayed up-regulations of PERK/eIF2α/ATF4/CHOP and
    ATF6/CHOP coupling with elevation of ER stress chaperones GRP78, GRP94, calnexin,
    calreticulin and PDI, implicating the involvement of these factors in ER stress-mediated
    apoptosis induced by 11-dehydrosinulariolide. The abolishment of apoptotic events after
    pre-treatment with salubrinal indicated that ER stress-mediated apoptosis is also induced
    by 11-dehydrosinulariolide against melanoma cells. The data in this study suggest that
    11-dehydrosinulariolide potentially induces apoptosis against melanoma cells via
    mitochondrial dysregulation and ER stress pathways.
    Appears in Collections:[Department of Beauty Science] Papers

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