Chemopreventive effect of dietary curcumin on inflammation-induced colorectal carcinogenesis in mice.
METHODS
Curcumin is a polyphenol with a variety of pharmacologic effects. We evaluate the effect of dietary curcumin on the severity of repeated colitis-associated colorectal cancer.


RESULTS
Six-week-old C57BL/6 mice were randomized into two dietary groups: standard diet and curcumin at 0.6% diet. The mice were exposed to 15 cycles of 0.7% dextran sodium sulphate for 1 week followed by distilled water for 10 days. After curcumin diet, the disease activity index presented a statistical reduction in the last cycles, macroscopic tumors were not seen and the microscopic study showed minor neoplasic lesions with respect to standard diet-group. β-Catenin translocation to the cytoplasm and/or nucleus was observed in the tumor tissue, but this translocation and its intensity were significantly minor in the curcumin diet-DSS animals. Cytokines as tumor necrosis factor-α and IFN-γ were significantly diminished in DSS-animals fed with curcumin. Conversely, non-modification of p53 expression was observed and cyclo-oxygenase-2 and inducible nitric oxide synthase were significantly reduced in the curcumin diet-DSS group.


CONCLUSIONS
We demonstrate the protective/preventive effect of curcumin in the progression of colorectal cancer associated to colitis, which was correlated with a lowered immunoreactivity of ß-catenin, a non-modification of p53 expression, a reduction of proinflammatory cytokine levels and a decrease of inflammatory protein overexpression.
Villegas
Isabel
I
Department of Pharmacology, School of Pharmacy, University of Seville, Seville, Spain.
Sánchez-Fidalgo
Susana
S
de la Lastra
Catalina Alarcón
CA
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003474:Curcumin / Q000008:administration & dosage*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004032:Diet; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011230:Precancerous Conditions / Q000209:etiology / Q000378:metabolism*; D021381:Protein Transport; D011897:Random Allocation; D012720:Severity of Illness Index; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D016207:Cytokines; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D003474:Curcumin