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
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