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

Bach, S P, Williamson, S E, Marshman, E, Kumar, S, O'Dwyer, S T, Potten, C S and Watson, A J (2001) The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice. Journal of Gastrointestinal Surgery, 5 (1). pp. 91-97. ISSN 1091-255X

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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.

Item Type: Article
Uncontrolled Keywords: 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
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
University of East Anglia > Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Depositing User: Pure Connector
Date Deposited: 07 Jul 2014 14:42
Last Modified: 25 Jul 2018 09:45
URI: https://ueaeprints.uea.ac.uk/id/eprint/48951
DOI:

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