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

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.
AuthorsFu-Shin Chueh, Yung-Liang Chen, Shu-Chun Hsu, Jai-Sing Yang, Shu-Ching Hsueh, Bin-Chuan Ji, Hsu-Feng Lu, Jing-Gung Chung
JournalOncology reports (Oncol Rep) Vol. 29 Issue 2 Pg. 613-8 (Feb 2013) ISSN: 1791-2431 [Electronic] Greece
PMID23233170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Alkylating
  • BRCA1 Protein
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • triptolide
  • DNA Modification Methylases
  • MGMT protein, human
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • DNA-Activated Protein Kinase
  • Protein-Serine-Threonine Kinases
  • DNA Repair Enzymes
  • Antineoplastic Agents, Alkylating (pharmacology)
  • Ataxia Telangiectasia Mutated Proteins
  • BRCA1 Protein (genetics)
  • Cell Cycle Proteins (genetics)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Comet Assay
  • DNA Damage
  • DNA Modification Methylases (genetics)
  • DNA Repair (drug effects, genetics)
  • DNA Repair Enzymes (genetics)
  • DNA-Activated Protein Kinase (genetics)
  • DNA-Binding Proteins (genetics)
  • Diterpenes (pharmacology)
  • Down-Regulation (genetics)
  • Epoxy Compounds (pharmacology)
  • Gene Expression (drug effects)
  • Humans
  • Melanoma (genetics)
  • Phenanthrenes (pharmacology)
  • Protein-Serine-Threonine Kinases (genetics)
  • RNA, Messenger (genetics, metabolism)
  • Real-Time Polymerase Chain Reaction
  • Skin Neoplasms (genetics)
  • Tumor Suppressor Protein p53 (genetics)
  • Tumor Suppressor Proteins (genetics)

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