The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice.
AuthorsBach, Simon P
Williamson, Sarah E
O'Dwyer, Sarah T
Potten, Christopher S
Watson, A J
AffiliationCancer Research Campaign, Department of Epithelial Biology, The Paterson Institute, Christie Hospital, Withington, Manchester M20 4BX, UK. Sbach@picr.man.ac.uk
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AbstractThe 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.
CitationThe antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice., 5 (1):91-7 J. Gastrointest. Surg.
JournalJournal of Gastrointestinal Surgery
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