The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice

Simon P. Bach, Sarah E. Williamson, Emma Marshman, Shant Kumar, Sarah T. O'Dwyer, Christopher S. Potten, Alastair J. M. Watson

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The antioxidant pyrrolidinedithiocarbamate improves the therapeutic efficacy of 5-fluorouracil (5-FU) against HCT-15 colorectal cancer cell line xenografts in nude mice without increasing toxicity to normal intestinal or hematopoietic tissues. In the current study we have shown that a similar clinically licensed antioxidant, N-acetylcysteine (200 mg/kg), can modulate the activity of 5-FU (120 mg/kg) against HCT-15 tumor xenografts in nude mice. We demonstrate that this effect is accompanied by a sustained elevation in p53-independent apoptosis without accompanying alterations in cell cycle kinetics. Extensive tumor necrosis is also a prominent feature of treatment; however, no significant impairment of neovascularization as assessed by intratumor microvessel density occurred. We believe that the clinical efficacy of N-acetylcysteine as an adjunct to 5-FU in advanced colorectal cancer should be investigated further.
Original languageEnglish
Pages (from-to)91-97
Number of pages7
JournalJournal of Gastrointestinal Surgery
Issue number1
Publication statusPublished - 2001


  • Acetylcysteine
  • Adenocarcinoma
  • Animals
  • Antioxidants
  • Apoptosis
  • Colorectal Neoplasms
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Drug Synergism
  • Flow Cytometry
  • Fluorouracil
  • Free Radical Scavengers
  • Genes, p53
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

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