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.
Original language | English |
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Pages (from-to) | 91-97 |
Number of pages | 7 |
Journal | Journal of Gastrointestinal Surgery |
Volume | 5 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2001 |
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