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

2.50
Hdl Handle:
http://hdl.handle.net/10541/84148
Title:
The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice.
Authors:
Bach, Simon P; Williamson, Sarah E; Marshman, Emma; Kumar, Shant; O'Dwyer, Sarah T; Potten, Christopher S; Watson, A J
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.
Affiliation:
Cancer Research Campaign, Department of Epithelial Biology, The Paterson Institute, Christie Hospital, Withington, Manchester M20 4BX, UK. Sbach@picr.man.ac.uk
Citation:
The antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice., 5 (1):91-7 J. Gastrointest. Surg.
Journal:
Journal of Gastrointestinal Surgery
Issue Date:
2001
URI:
http://hdl.handle.net/10541/84148
PubMed ID:
11309653
Type:
Article
Language:
en
ISSN:
1091-255X
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBach, Simon Pen
dc.contributor.authorWilliamson, Sarah Een
dc.contributor.authorMarshman, Emmaen
dc.contributor.authorKumar, Shanten
dc.contributor.authorO'Dwyer, Sarah Ten
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorWatson, A Jen
dc.date.accessioned2009-10-13T10:47:54Z-
dc.date.available2009-10-13T10:47:54Z-
dc.date.issued2001-
dc.identifier.citationThe antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice., 5 (1):91-7 J. Gastrointest. Surg.en
dc.identifier.issn1091-255X-
dc.identifier.pmid11309653-
dc.identifier.urihttp://hdl.handle.net/10541/84148-
dc.description.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.en
dc.language.isoenen
dc.subjectColorectal Canceren
dc.subjectCancer Transplantationen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAcetylcysteine-
dc.subject.meshAdenocarcinoma-
dc.subject.meshAnimals-
dc.subject.meshAntioxidants-
dc.subject.meshApoptosis-
dc.subject.meshColorectal Neoplasms-
dc.subject.meshDisease Models, Animal-
dc.subject.meshDrug Evaluation, Preclinical-
dc.subject.meshDrug Synergism-
dc.subject.meshFlow Cytometry-
dc.subject.meshFluorouracil-
dc.subject.meshFree Radical Scavengers-
dc.subject.meshGenes, p53-
dc.subject.meshImmunohistochemistry-
dc.subject.meshIn Situ Nick-End Labeling-
dc.subject.meshMice-
dc.subject.meshMice, Nude-
dc.subject.meshNeoplasm Transplantation-
dc.subject.meshTransplantation, Heterologous-
dc.subject.meshTumor Cells, Cultured-
dc.titleThe antioxidant n-acetylcysteine increases 5-fluorouracil activity against colorectal cancer xenografts in nude mice.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign, Department of Epithelial Biology, The Paterson Institute, Christie Hospital, Withington, Manchester M20 4BX, UK. Sbach@picr.man.ac.uken
dc.identifier.journalJournal of Gastrointestinal Surgeryen

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