Role of endonucleases XPF and XPG in nucleotide excision repair of platinated DNA and cisplatin/oxaliplatin cytotoxicity

Chembiochem. 2011 May 2;12(7):1115-23. doi: 10.1002/cbic.201000724. Epub 2011 Mar 30.

Abstract

Resistance of tumor cells to platinum anticancer agents poses a major problem in cancer chemotherapy. One of the mechanisms associated with platinum-based drug resistance is the enhanced capacity of the cell to carry out nucleotide excision repair (NER) on platinum-damaged DNA. Endonucleases XPF and XPG are critical components of NER, responsible for excising the damaged DNA strand to remove the DNA lesion. Here, we investigated possible consequences of down-regulation of XPF and XPG gene expression in osteosarcoma cancer cells (U2OS) and the impact on cellular transcription and DNA repair. We further evaluated the sensitivity of such cells toward the platinum anticancer drugs cisplatin and oxaliplatin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology*
  • Cytotoxins / pharmacology
  • DNA Damage / drug effects*
  • DNA Repair*
  • Drug Screening Assays, Antitumor
  • Endonucleases / chemistry
  • Endonucleases / genetics
  • Endonucleases / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Organoplatinum Compounds / pharmacology*
  • Osteosarcoma / enzymology
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Oxaliplatin

Substances

  • Antineoplastic Agents
  • Cytotoxins
  • Organoplatinum Compounds
  • Oxaliplatin
  • Endonucleases
  • Cisplatin