| Novel quinolone CHM-1 induces apoptosis and inhibits metastasis in a human osterogenic sarcoma cell line. | |
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MedLine Citation:
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PMID: 19557855 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Shu-Chun Hsu; Jai-Sing Yang; Chao-Lin Kuo; Chyi Lo; Jing-Pin Lin; Te-Chun Hsia; Jen-Jyh Lin; Kuang-Chi Lai; Hsiu-Maan Kuo; Li-Jiau Huang; Sheng-Chu Kuo; W Gibson Wood; Jing-Gung Chung |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of orthopaedic research : official publication of the Orthopaedic Research Society Volume: 27 ISSN: 1554-527X ISO Abbreviation: J. Orthop. Res. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-28 Completed Date: 2010-09-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8404726 Medline TA: J Orthop Res Country: United States |
Other Details:
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Languages: eng Pagination: 1637-44 Citation Subset: IM |
Affiliation:
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School of Nutrition, China Medical University, Taichung, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Bone Neoplasms / drug therapy*, genetics, pathology Caspases / antagonists & inhibitors, biosynthesis Cell Line, Tumor Cell Movement / drug effects Cell Survival / drug effects Comet Assay DNA Damage Dioxoles / pharmacology* Drug Screening Assays, Antitumor Enzyme Inhibitors / pharmacology Gene Expression / drug effects Humans MAP Kinase Signaling System / drug effects Matrix Metalloproteinase 9 / antagonists & inhibitors* Mitogen-Activated Protein Kinases / metabolism Osteosarcoma / drug therapy*, genetics, pathology Quinolones / pharmacology* Reactive Oxygen Species / metabolism |
| Chemical | |
Reg. No./Substance:
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0/2'-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone; 0/Antineoplastic Agents; 0/Dioxoles; 0/Enzyme Inhibitors; 0/Quinolones; 0/Reactive Oxygen Species; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspases; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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