Induction of DNA damage by deguelin is mediated through reducing DNA repair genes in human non-small cell lung cancer NCI-H460 cells
Autor: | Yang-Ching Ko, Jen Jyh Lin, Te Chun Hsia, Chien Chih Yu, Su Tso Yang, Bin-Chuan Ji, Jing Gung Chung, Jai Sing Yang, Tung-Yuan Lai, Kuang-Chi Lai |
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Rok vydání: | 2012 |
Předmět: |
Cancer Research
Lung Neoplasms Time Factors DNA damage DNA repair Down-Regulation Antineoplastic Agents Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins DNA-Activated Protein Kinase Protein Serine-Threonine Kinases Biology Real-Time Polymerase Chain Reaction chemistry.chemical_compound comet assay Carcinoma Non-Small-Cell Lung Cell Line Tumor Rotenone Humans RNA Messenger deguelin DNA Modification Methylases Electrophoresis Agar Gel Dose-Response Relationship Drug BRCA1 Protein Tumor Suppressor Proteins Nuclear Proteins Articles General Medicine Cell cycle DNA repair protein XRCC4 Flow Cytometry Molecular biology human lung cancer NCI-H460 cells DNA-Binding Proteins Gene Expression Regulation Neoplastic Comet assay DNA Repair Enzymes Real-time polymerase chain reaction DNA Topoisomerases Type I Oncology chemistry Cancer research DNA fragmentation Tumor Suppressor Protein p53 Deguelin |
Zdroj: | Oncology Reports |
ISSN: | 1791-2431 1021-335X |
Popis: | It has been shown that deguelin, one of the compounds of rotenoids from flavonoid family, induced cytotoxic effects through induction of cell cycle arrest and apoptosis in many types of human cancer cell lines, but deguelin-affected DNA damage and repair gene expression (mRNA) are not clarified yet. We investigated the effects of deguelin on DNA damage and associated gene expression in human lung cancer NCI-H460 cells in vitro. DNA damage was assayed by using the comet assay and DNA gel electrophoresis and the results indicated that NCI-H460 cells treated with 0, 50, 250 and 500 nM deguelin led to a longer DNA migration smear based on the single cell electrophoresis and DNA fragmentation occurred based on the examination of DNA gel electrophoresis. DNA damage and repair gene expression (mRNA) were evaluated by using real-time PCR assay and the results indicated that 50 and 250 nM deguelin for a 24-h exposure in NCI-H460 cells, decreased the gene levels of breast cancer 1, early onset (BRCA1), DNA-dependent serine/threonine protein kinase (DNA-PK), O6-methylguanine-DNA methyltransferase (MGMT), p53, ataxia telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) mRNA expressions. Collectively, the present study showed that deguelin caused DNA damage and inhibited DNA damage and repair gene expressions, which might be due to deguelin-inhibited cell growth in vitro. |
Databáze: | OpenAIRE |
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