Abstract
20-Fluoro-6,7-methylenedioxy-2-phenyl-4-quino-lone (CHM-1) has been reported to induce cell cycle arrest and apoptosis in many types of cancer cells. However, there is no available information to show CHM-1 affecting DNA damage and expression of associated repair genes. Herein, we investigated whether or not CHM-1 induced DNA damage and affected DNA repair gene expression in U-2 OS human osterogenic sarcoma cells. The comet assay showed that incubation of U-2 OS cells with 0, 0.75, 1.5, 3 and 6 μM of CHM-1 led to a longer DNA migration smear (comet tail). DNA gel electrophoresis showed that 3 μM of CHM-1 for 24 and 48 h treatment induced DNA fragmentation in U-2 OS cells. Real-time PCR analysis showed that treatment with 3 μM of CHM-1 for 24 h reduced the mRNA expression levels of ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), breast cancer 1, early onset (BRCA1), 14-3-3sigma (14-3-3σ), DNA-dependent serine/threonine protein kinase (DNA-PK) and O(6)-methylguanine-DNA methyltransferase (MGMT) genes in a time-dependent manner. Taken together, the results indicate that CHM-1 caused DNA damage and reduced DNA repair genes in U-2 OS cells, which may be the mechanism for CHM-1-inhibited cell growth and induction of apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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14-3-3 Proteins / biosynthesis
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14-3-3 Proteins / genetics
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Ataxia Telangiectasia Mutated Proteins
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BRCA1 Protein / biosynthesis
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BRCA1 Protein / genetics
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Biomarkers, Tumor / biosynthesis
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Biomarkers, Tumor / genetics
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Bone Neoplasms / drug therapy*
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Bone Neoplasms / genetics
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Cell Cycle Proteins / biosynthesis
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Cell Cycle Proteins / genetics
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Cell Line, Tumor
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Comet Assay
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DNA Damage*
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DNA Fragmentation / drug effects
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DNA Modification Methylases / biosynthesis
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DNA Modification Methylases / genetics
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DNA Repair / drug effects*
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DNA Repair / genetics
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DNA Repair Enzymes / biosynthesis
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DNA Repair Enzymes / genetics
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DNA-Activated Protein Kinase / biosynthesis
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DNA-Activated Protein Kinase / genetics
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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Dioxoles / pharmacology*
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Exonucleases / biosynthesis
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Exonucleases / genetics
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Exoribonucleases
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Gene Expression / drug effects
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Humans
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Osteosarcoma / drug therapy*
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Osteosarcoma / genetics
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Protein Serine-Threonine Kinases / biosynthesis
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Protein Serine-Threonine Kinases / genetics
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Quinolones / pharmacology*
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Tumor Suppressor Proteins / biosynthesis
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Tumor Suppressor Proteins / genetics
Substances
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14-3-3 Proteins
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2'-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone
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BRCA1 Protein
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BRCA1 protein, human
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Biomarkers, Tumor
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Cell Cycle Proteins
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DNA-Binding Proteins
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Dioxoles
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Quinolones
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Tumor Suppressor Proteins
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DNA Modification Methylases
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MGMT protein, human
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ATM protein, human
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ATR protein, human
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Ataxia Telangiectasia Mutated Proteins
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DNA-Activated Protein Kinase
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Protein Serine-Threonine Kinases
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Exonucleases
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Exoribonucleases
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SFN protein, human
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DNA Repair Enzymes