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. and Watson, Alastair J. M. (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
Depositing User: Pure Connector
Date Deposited: 07 Jul 2014 13:42
Last Modified: 05 May 2020 23:50
URI: https://ueaeprints.uea.ac.uk/id/eprint/48951
DOI: 10.1016/S1091-255X(01)80018-4

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