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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/16380


    Title: Novel quinolone CHM-1 induces apoptosis and inhibits metastasis in a human osterogenic sarcoma cell line
    Authors: 徐素琴;Hsu, Shu-Chun;楊家欣;Yang, Jai-Sing;郭昭麟;Kuo, Chao-Lin;羅琦;Lo, Chyi;林景彬;Lin, Jing-Pin;夏德椿;Hsia, Te-Chun;Lin, Jen-Jyh;Lai, Kuang-Chi;郭秀滿;Kuo, Hsiu-Maan;Huang, Li-Jiau;郭盛助;Kuo, Sheng-Chu;Wood, W.Gibson;鍾景光;Chung, Jing-Gung
    Contributors: 生物科技學系
    Date: 2009-12
    Issue Date: 2012-11-23 17:12:18 (UTC+8)
    Abstract: Novel 2-phenyl-4-quinolone compounds have potent cytotoxic effects on different human cancer cell lines. In this study, we examined anticancer activity and mechanisms of 20-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone (CHM-1) in human osterogenic sarcoma U-2 OS cells. CHM-1-induced apoptosis was determined by flow cytometric analysis, DAPI staining, Comet assay, and caspase inhibitors. CHM-1-inhibited cell migration and invasion was assessed by a wound healing assay, gelatin zymography, and a Transwell assay. The mechanisms of CHM-1 effects on apoptosis and metastasis signaling pathways were studied using Western blotting and gene expression. CHM-1 induced G2/M arrest and apoptosis at an IC(50) (3 microM) in U-2 OS cells and caspase-3, -8, and -9 were activated. Caspase inhibitors increased cell viability after exposure to CHM-1. CHM-1-induced apoptosis was associated with enhanced ROS generation, DNA damage, decreased DeltaPsi(m) levels, and promotion of mitochondrial cytochrome c release. CHM-1 stimulated mRNA expression of caspase-3, -8, and -9, AIF, and Endo G. In addition, CHM-1 inhibited cell metastasis at a low concentration (<3 microM). CHM-1 inhibited the cell metastasis through the inhibition of MMP-2, -7, and -9. CHM-1 also decreased the levels of MAPK signaling pathways before leading to the inhibition of MMPs. In summary, CHM-1 is a potent inducer of apoptosis, which plays a role in the anticancer activity of CHM-1.
    Relation: JOURNAL OF ORTHOPAEDIC RESEARCH;27(12):1637-44.
    Appears in Collections:[生物科技學系] 期刊論文

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