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Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation‐associated mouse colon carcinogenesis
Author(s) -
Murakami Akira,
Furukawa Ikuyo,
Miyamoto Shingo,
Tanaka Takuji,
Ohigashi Hajime
Publication year - 2012
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.1054
Subject(s) - curcumin , azoxymethane , carcinogenesis , nitric oxide synthase , nitric oxide , colitis , chemistry , inflammation , pharmacology , colorectal cancer , cancer research , lipopolysaccharide , cancer , medicine , biochemistry , immunology , gene , organic chemistry
Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We recently reported that ar‐turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the present study, we explored the molecular mechanisms by which ATM attenuates NO generation and examined the anti‐carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)‐induced expression of inducible forms of both nitric oxide synthase and cyclooxygenase (iNOS and COX‐2, respectively). A chase experiment using actinomycin D revealed that ATM accelerated the decay of iNOS and COX‐2 mRNA, suggesting a post‐transcriptional mechanism. ATM prevented LPS‐induced translocation of HuR, an AU‐rich element‐binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model, oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)‐induced shortening of the large bowel by 52–58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR, and their combinations using a model of dimethylhydradine‐initiated and DSS‐promoted mouse colon carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both doses suppressed adenocarcinoma multiplicity by 63–69%. Interestingly, the combination of CUR and TUR at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination with CUR may become a powerful method for prevention of inflammation‐associated colon carcinogenesis. © 2012 BioFactors, 2013