The novel quinolone CHM-1 induces DNA damage and inhibits DNA repair gene expressions in a human osterogenic sarcoma cell line.

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.

• Authors: Hung-Yi Chen, Hsu-Feng Lu, Jai-Sing Yang, Sheng-Chu Kuo, Chyi Lo, Mei-Due Yang, Tsan-Hung Chiu, Fu-Shin Chueh, Heng-Chien Ho, Yang-Ching Ko, Jing-Gung Chung
• Journal: Anticancer research (Anticancer Res) Vol. 30 Issue 10 Pg. 4187-92 (Oct 2010) ISSN: 1791-7530 [Electronic] Greece
• PMID: 21036739 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 14-3-3 Proteins
• 2'-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone
• BRCA1 Protein
• BRCA1 protein, human
• Biomarkers, Tumor
• Cell Cycle Proteins
• DNA-Binding Proteins
• Dioxoles
• Quinolones
• Tumor Suppressor Proteins
• DNA Modification Methylases
• MGMT protein, human
• ATM protein, human
• ATR protein, human
• Ataxia Telangiectasia Mutated Proteins
• DNA-Activated Protein Kinase
• Protein Serine-Threonine Kinases
• Exonucleases
• Exoribonucleases
• SFN protein, human
• DNA Repair Enzymes

Topics

• 14-3-3 Proteins (biosynthesis, genetics)
• Ataxia Telangiectasia Mutated Proteins
• BRCA1 Protein (biosynthesis, genetics)
• Biomarkers, Tumor (biosynthesis, genetics)
• Bone Neoplasms (drug therapy, genetics)
• Cell Cycle Proteins (biosynthesis, genetics)
• Cell Line, Tumor
• Comet Assay
• DNA Damage
• DNA Fragmentation (drug effects)
• DNA Modification Methylases (biosynthesis, genetics)
• DNA Repair (drug effects, genetics)
• DNA Repair Enzymes (biosynthesis, genetics)
• DNA-Activated Protein Kinase (biosynthesis, genetics)
• DNA-Binding Proteins (biosynthesis, genetics)
• Dioxoles (pharmacology)
• Exonucleases (biosynthesis, genetics)
• Exoribonucleases
• Gene Expression (drug effects)
• Humans
• Osteosarcoma (drug therapy, genetics)
• Protein Serine-Threonine Kinases (biosynthesis, genetics)
• Quinolones (pharmacology)
• Tumor Suppressor Proteins (biosynthesis, genetics)