No prevention of liver and kidney tumors in Long-Evans Cinnamon rats by dietary curcumin, but inhibition at other sites and of metastases

被引:57
作者
Frank, N
Knauft, J
Amelung, F
Nair, J
Wesch, H
Bartsch, H
机构
[1] German Canc Res Ctr, Div Toxicol & Canc Risk Factors, D-69120 Heidelberg, Germany
[2] German Canc Res Ctr, Div Cellular & Mol Pathol, D-69120 Heidelberg, Germany
[3] German Canc Res Ctr, Div Oncol Diagnost & Therapy, D-69120 Heidelberg, Germany
关键词
LEC rats; curcumin; chemoprevention; carcinogenesis; copper toxicity;
D O I
10.1016/S0027-5107(02)00328-7
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Long-Evans Cinnamon (LEC) rats, an inbred mutant strain which accumulates copper due to an aberrant copper-transporting ATPase gene, develop acute hepatitis, chronic liver injury and liver tumors as a result of copper-induced oxidative stress, lipid peroxidation and DNA damage. Curcumin, an antioxidant and anti-inflammatory agent, has shown anticancer properties in many rodent models. We investigated the modulating role of curcumin in liver and kidney carcinogenesis in LEC rats. Two groups of 4-week-old LEC rats (n = 60 each) were fed either a standard diet (control) or received 0.5% curcumin in the diet for life. In untreated LEC rats, the rate of acute liver failure, the incidence of liver tumors and of kidney tumors were 32, 100 and 10% respectively, which was not altered by curcumin treatment. However, curcumin reduced tumor incidence at other organ sites (15% versus 0%; P = 0.025) and suppressed formation of metastases (18% versus 0%; P = 0.01). Median survival time was decreased from 88.7 to 78.1 weeks in curcumin-treated rats (P = 0.002). The lack of chemoprevention of liver and kidney tumors in LEC rats by curcumin may be caused by enhanced toxicity and oxidative stress due to excess copper. We conclude that curcumin should be contra-indicated for patients suffering from inherited and acquired metal storage diseases that include patients with hepatitis C virus infection. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
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页码:127 / 135
页数:9
相关论文
共 53 条
[1]   Curcumin is an in vivo inhibitor of angiogenesis [J].
Arbiser, JL ;
Klauber, N ;
Rohan, R ;
van Leeuwen, R ;
Huang, MT ;
Fisher, C ;
Flynn, E ;
Byers, HR .
MOLECULAR MEDICINE, 1998, 4 (06) :376-383
[2]   Ultrasensitive and specific detection methods for exocylic DNA adducts: Markers for lipid peroxidation and oxidative stress [J].
Bartsch, H ;
Nair, J .
TOXICOLOGY, 2000, 153 (1-3) :105-114
[3]   CURCUMIN, AN ANTITUMOR PROMOTER AND ANTIINFLAMMATORY AGENT, INHIBITS INDUCTION OF NITRIC-OXIDE SYNTHASE IN ACTIVATED MACROPHAGES [J].
BROUET, I ;
OHSHIMA, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 206 (02) :533-540
[4]   In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties [J].
Chan, MMY ;
Huang, HI ;
Fenton, MR ;
Fong, D .
BIOCHEMICAL PHARMACOLOGY, 1998, 55 (12) :1955-1962
[5]   Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis [J].
Chuang, SE ;
Kuo, ML ;
Hsu, CH ;
Chen, CR ;
Lin, JK ;
Lai, GM ;
Hsieh, CY ;
Cheng, AL .
CARCINOGENESIS, 2000, 21 (02) :331-335
[6]   Effect of curcumin on the aryl hydrocarbon receptor and cytochrome P450 1A1 in MCF-7 human breast carcinoma cells [J].
Ciolino, HP ;
Daschner, PJ ;
Wang, TTY ;
Yeh, GC .
BIOCHEMICAL PHARMACOLOGY, 1998, 56 (02) :197-206
[7]   Curcumin modifies Apcmin apoptosis resistance and inhibits 2-amino 1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced tumour formation in Apcmin mice [J].
Collett, GP ;
Robson, CN ;
Mathers, JC ;
Campbell, FC .
CARCINOGENESIS, 2001, 22 (05) :821-825
[8]  
Frank Norbert, 2002, Proceedings of the American Association for Cancer Research Annual Meeting, V43, P867
[9]   EFFECT OF TURMERIC ON XENOBIOTIC-METABOLIZING ENZYMES [J].
GOUD, VK ;
POLASA, K ;
KRISHNASWAMY, K .
PLANT FOODS FOR HUMAN NUTRITION, 1993, 44 (01) :87-92
[10]   Interaction of the copper chaperone HAH1 with the Wilson disease protein is essential for copper homeostasis [J].
Hamza, I ;
Schaefer, M ;
Klomp, LWJ ;
Gitlin, JD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (23) :13363-13368