The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice.
Bach, Simon P Williamson, Sarah E Marshman, Emma Kumar, Shant O'Dwyer, Sarah T Potten, Christopher S Watson, A J
Bach, Simon P
Williamson, Sarah E
Marshman, Emma
Kumar, Shant
O'Dwyer, Sarah T
Potten, Christopher S
Watson, A J
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Abstract
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.
Description
Date
2001
Publisher
Keywords
Colorectal Cancer
Cancer Transplantation
Cultured Tumour Cells
Cancer Transplantation
Cultured Tumour Cells
Type
Article
Citation
The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice., 5 (1):91-7 J. Gastrointest. Surg.