title: Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation-associated mouse colon carcinogenesis.
abstract: 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.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. cancer@kais.kyoto-u.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Furukawa
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohigashi
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D030024:Curcuma; D003474:Curcumin / Q000627:therapeutic use*; D005260:Female; D007659:Ketones / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000627:therapeutic use*
chemical_list: D007659:Ketones; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012717:Sesquiterpenes; C078098:ar-turmerone; C012596:turmeric extract; D003474:Curcumin