Antioxidants enhance the susceptibility of colon carcinoma cells to 5-fluorouracil by augmenting the induction of the bax protein.
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.
Adeyemo
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Academic Department of Surgery, Royal Free and University College London Medical School, Pond Street, London NW3 2QG, UK. dhoyho@compuserve.com
Imtiaz
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F
Toffa
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S
Lowdell
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M
Wickremasinghe
R G
RG
Winslet
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M
D000111:Acetylcysteine / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis; D015153:Blotting, Western; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D004347:Drug Interactions; D005434:Flow Cytometry; D005472:Fluorouracil / Q000627:therapeutic use*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D010084:Oxidation-Reduction; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; C494826:BAX protein, human; D016166:Free Radical Scavengers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D014810:Vitamin E; D005472:Fluorouracil; D000111:Acetylcysteine