No prevention of liver and kidney tumors in Long-Evans Cinnamon rats by dietary curcumin, but inhibition at other sites and of metastases.
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.
Frank
Norbert
N
Division of Toxicology and Cancer Risk Factors, German Cancer Research Center (DKFZ), lm Neuenheimer Feld 280, 69120 Heidelberg, Germany. n.frank@dkfz.de
Knauft
Jutta
J
Amelung
Folker
F
Nair
Jagadeesan
J
Wesch
Horst
H
Bartsch
Helmut
H
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003474:Curcumin / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000473:pathology*; D008113:Liver Neoplasms / Q000473:pathology*; D008175:Lung Neoplasms / Q000517:prevention & control*; D008297:Male; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D051381:Rats; D020318:Rats, Long-Evans
D000970:Antineoplastic Agents; D003474:Curcumin