Antioxidants enhance the susceptibility of colon carcinoma cells to 5-fluorouracil by augmenting the induction of the bax protein

被引:23
作者
Adeyemo, D
Imtiaz, F
Toffa, S
Lowdell, M
Wickremasinghe, RG
Winslet, M
机构
[1] UCL Royal Free & UCL Med Sch, Acad Dept Surg, London NW3 2QG, England
[2] UCL Royal Free & UCL Med Sch, Acad Dept Haematol, London NW3 2QG, England
关键词
apoptosis; bax; colorectal neoplasms; reactive oxygen species; antioxidant;
D O I
10.1016/S0304-3835(00)00720-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 EU in the colorectal cancer cell lines cole 201 and cole 205. This suggests that reduction of intracellular levels of reactive oxygen species enhance susceptibility to 5 FU (apoptotic stimuli) by augmentation of bax expression. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:77 / 84
页数:8
相关论文
共 37 条
[1]   The Bcl-2 protein family: Arbiters of cell survival [J].
Adams, JM ;
Cory, S .
SCIENCE, 1998, 281 (5381) :1322-1326
[2]   Death receptors: Signaling and modulation [J].
Ashkenazi, A ;
Dixit, VM .
SCIENCE, 1998, 281 (5381) :1305-1308
[3]   Epidermal growth factor (EGF)-induced generation of hydrogen peroxide - Role in EGF receptor-mediated tyrosine phosphorylation [J].
Bae, YS ;
Kang, SW ;
Seo, MS ;
Baines, IC ;
Tekle, E ;
Chock, PB ;
Rhee, SG .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (01) :217-221
[4]  
BOERSMA WM, 1992, CYTOMETRY, V27, P275
[5]  
Chinery R, 1998, CANCER RES, V58, P2323
[6]   Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: A p53-independent induction of p21(WAF1/CIP1) via C/EBP beta [J].
Chinery, R ;
Brockman, JA ;
Peeler, MO ;
Shyr, Y ;
Beauchamp, RD ;
Coffey, RJ .
NATURE MEDICINE, 1997, 3 (11) :1233-1241
[7]   APOPTOSIS IN CANCER-THERAPY - CROSSING THE THRESHOLD [J].
FISHER, DE .
CELL, 1994, 78 (04) :539-542
[8]   DIRECT EVIDENCE FOR TUMOR NECROSIS FACTOR-INDUCED MITOCHONDRIAL REACTIVE OXYGEN INTERMEDIATES AND THEIR INVOLVEMENT IN CYTOTOXICITY [J].
GOOSSENS, V ;
GROOTEN, J ;
DEVOS, K ;
FIERS, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (18) :8115-8119
[9]   Randomised controlled trial of faecal-occult-blood screening for colorectal cancer [J].
Hardcastle, JD ;
Chamberlain, JO ;
Robinson, MHE ;
Moss, SM ;
Amar, SS ;
Balfour, TW ;
James, PD ;
Mangham, CM .
LANCET, 1996, 348 (9040) :1472-1477
[10]   The biochemistry of apoptosis [J].
Hengartner, MO .
NATURE, 2000, 407 (6805) :770-776