Meiho University Institutional Repository:Item 987654321/2191
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    题名: Sinulariolide Induced Hepatocellular Carcinoma Apoptosisthrough Activation of Mitochondrial-Related Apoptotic andPERK/eIF2α/ATF4/CHOP Pathway
    作者: Yi-Jen Chen;Jui-Hsin Su;Chia-Yu Tsao;Chun-Tzu Hung;Hsiang-Hao Chao;Jen-Jie Lin;Ming-Hui Liao;Zih-Yan Yang;Han Hisang Huang;Feng-Jen Tsai;Shun-Hsiang Weng;Yu-Jen Wu
    贡献者: 健康暨護理學院
    日期: 2013
    上传时间: 2013-10-11T07:39:28Z (UTC)
    摘要: Sinulariolide, an active compound isolated from the cultured soft coral Sinularia
    flexibilis, has potent anti-microbial and anti-tumorigenesis effects towards melanoma
    and bladder cancer cells. In this study, we investigated the effects of sinulariolide on
    hepatocellular carcinoma (HCC) cell growth and protein expression. Sinulariolide
    suppressed the proliferation and colony formation of HCC HA22T cells in a
    dose-dependent manner and induced both early and late apoptosis according to flow
    cytometry, Annexin V/PI stain and TUNEL/DAPI stain analyses. A mechanistic analysis
    demonstrated that sinulariolide-induced apoptosis was activated through a
    mitochondria-related pathway, showing up-regulation of Bax, Bad and AIF, and downregulation
    of Bcl-2, Bcl-xL, MCl-1 and p-Bad. Sinulariolide treatment led to loss of the
    mitochondrial membrane potential, release of mitochondrial cytochrome c to the cytosol,
    and activation of both caspase-9 and caspase-3. Sinulariolide-induced apoptosis was
    significantly blocked by the caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK. The
    increased expression of cleaved PARP also suggested that caspase-independent apoptotic
    pathway was involved. In the western blotting; the elevation of ER chaperones GRP78;
    GRP94; and CALR; as well as up-regulations of PERK/eIF2α/ATF4/CHOP; and diminished
    cell death with pre-treatment of eIF2α phosphatase inhibitor; salubrinal; implicated the
    involvement of ER stress-mediated PERK/eIF2α/ATF4/CHOP apoptotic pathway following
    sinulariolide treatment in hepatoma cells. The current study suggested sinulariolide-induced
    hepatoma cell cytotoxicity involved multiple apoptotic signal pathways. This may implicate
    that sinulariolide is a potential compound for the treatment of hepatocellular carcinoma.
    關聯: molecules
    显示于类别:[美容系] 期刊論文

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