Triptolide induced DNA damage in A375.S2 human malignant melanoma cells is mediated via reduction of DNA repair genes

Chueh,Fu-Shin; Chen,Yung-Liang; Hsu,Shu-Chun; Yang,Jai-Sing; Hsueh,Shu-Ching; Ji,Bin-Chuan; Lu,Hsu-Feng; Chung,Jing-Gung

doi:10.3892/or.2012.2170

Triptolide induced DNA damage in A375.S2 human malignant melanoma cells is mediated via reduction of DNA repair genes

Authors:
- Fu-Shin Chueh
- Yung-Liang Chen
- Shu-Chun Hsu
- Jai-Sing Yang
- Shu-Ching Hsueh
- Bin-Chuan Ji
- Hsu-Feng Lu
- Jing-Gung Chung
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Affiliations: Departments of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan, R.O.C., Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu 300, Taiwan, R.O.C., Departments of Nutrition, China Medical University, Taichung 404, Taiwan, R.O.C., Departments of Pharmacology, China Medical University, Taichung 404, Taiwan, R.O.C., Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei 112, Taiwan, R.O.C., Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua 500, Taiwan, R.O.C., Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei 112, Taiwan, R.O.C., Departments of Biological Science and Technology, China Medical University, Taichung 404, Taiwan, R.O.C.
Published online on: December 7, 2012 https://doi.org/10.3892/or.2012.2170
Pages: 613-618

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Abstract

Numerous studies have demonstrated that triptolide induces cell cycle arrest and apoptosis in human cancer cell lines. However, triptolide-induced DNA damage and inhibition of DNA repair gene expression in human skin cancer cells has not previously been reported. We sought the effects of triptolide on DNA damage and associated gene expression in A375.S2 human malignant melanoma cells in vitro. Comet assay, DAPI staining and DNA gel electrophoresis were used for examining DNA damage and results indicated that triptolide induced a longer DNA migration smear based on single cell electrophoresis and DNA condensation and damage occurred based on the examination of DAPI straining and DNA gel electrophoresis. The real-time PCR technique was used to examine DNA damage and repair gene expression (mRNA) and results indicated that triptolide led to a decrease in the ataxia telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR), breast cancer 1, early onset (BRCA-1), p53, DNA-dependent serine/threonine protein kinase (DNA-PK) and O6-methylguanine-DNA methyltransferase (MGMT) mRNA expression. Thus, these observations indicated that triptolide induced DNA damage and inhibited DNA damage and repair-associated gene expression (mRNA) that may be factors for triptolide-mediated inhibition of cell growth in vitro in A375.S2 cells.

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