Abstract
5 Fluorouracil (5 FU), the most effective systemic chemotherapeutic agent in the management of advanced colorectal carcinoma acts by inducing apoptosis. Response rates, approximately 20% is improved by folinic acid. This study investigates similar modulation of 5 FU-induced apoptosis by oxidant quenching. A five-fold reduction of intracellular oxidant levels by antioxidants N-acetylcysteine and vitamin E did not induce apoptosis, it however augmented pro-apoptotic bax protein expression, and apoptotic response to a non-toxic dose of 5 FU in the colorectal cancer cell lines colo 201 and colo 205. This suggests that reduction of intracellular levels of reactive oxygen species enhance susceptibility to 5 FU (apoptotic stimuli) by augmentation of bax expression.
MeSH terms
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Acetylcysteine / pharmacology
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Antimetabolites, Antineoplastic / therapeutic use
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Antioxidants / therapeutic use*
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Apoptosis
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Blotting, Western
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / genetics*
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Drug Interactions
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Flow Cytometry
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Fluorouracil / therapeutic use*
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Free Radical Scavengers / pharmacology
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Humans
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Oxidation-Reduction
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Proto-Oncogene Proteins / biosynthesis*
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Proto-Oncogene Proteins c-bcl-2*
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Reactive Oxygen Species
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Time Factors
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Tumor Cells, Cultured
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Vitamin E / pharmacology
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bcl-2-Associated X Protein
Substances
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Antimetabolites, Antineoplastic
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Antioxidants
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BAX protein, human
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Free Radical Scavengers
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Reactive Oxygen Species
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bcl-2-Associated X Protein
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Vitamin E
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Fluorouracil
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Acetylcysteine