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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/16859


    Title: Safrole Induces G0/G1 Phase Arrest via Inhibition of Cyclin E and Provokes Apoptosis through Endoplasmic Reticulum Stress and Mitochondrion-dependent Pathways in Human Leukemia HL-60 Cells
    Authors: 闕甫伈;Chueh, Fu-Shin;鍾景光;Chung, Jing-Gung
    Contributors: 生物科技學系
    Keywords: Safrole;human leukemia HL-60 cells;apoptosis;ER stress;mitochondria;HSC-3 cells.
    Date: 2012-04
    Issue Date: 2012-11-23 17:17:47 (UTC+8)
    Abstract: Safrole, a component of Piper betle inflorescence, is a carcinogen which has been demonstrated to induce apoptosis on human oral cancer HSC-3 cells in vitro and to inhibit HSC-3 cells in xenograft tumor cells in vivo. In our previous study, safrole promoted phagocytosis by macrophages and natural killer cell cytotoxicity in normal BALB/c mice. The cytotoxic effects of safrole on HL-60 cells were investigated by using flow cytometric analysis, comet assay, 4',6-diamidino-2-phenylindole (DAPI) staining, western blotting and confocal laser microscopy. The obtained results indicate that safrole induced a cytotoxic response through reducing the percentage of viable cells and induction of apoptosis in HL-60 cells in a dose-dependent manner. DAPI staining and comet assay also showed that safrole induced apoptosis (chromatin condensation) and DNA damage in HL-60 cells. The flow cytometric assay showed that safrole increased the production of reactive oxygen species (ROS) and Ca(2+) and reduced the mitochondrial membrane potential in HL-60 cells. Safrole enhanced the levels of the pro-apoptotic protein BAX, inhibited those of the anti-apoptotic protein BCL-2 and promoted the levels of apoptosis-inducing factor (AIF) and endonuclease G (Endo G) in HL-60 cells. Furthermore, safrole promoted the expression of glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153) and of activating transcription factor 6α (ATF-6α). Based on these findings, we suggest that safrole-induced apoptosis in HL-60 cells is mediated through the ER stress and intrinsic signaling pathways.
    Relation: ANTICANCER RESEARCH, 32(5):1671-9.
    Appears in Collections:[生物科技學系] 期刊論文

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