title: The rice bran constituent tricin potently inhibits cyclooxygenase enzymes and interferes with intestinal carcinogenesis in ApcMin mice.
abstract: While brown rice is a staple dietary constituent in Asia, rice consumed in the Western world is generally white, obtained from brown rice by removal of the bran. Rice bran contains the flavone tricin, which has been shown to inhibit colon cancer cell growth. We tested the hypothesis that tricin interferes with adenoma formation in the Apc(Min) mouse. Mice received tricin (0.2%) in their American Institute of Nutrition 93G diet throughout their postweaning life span (4-18 weeks). Consumption of tricin reduced numbers of intestinal adenomas by 33% (P < 0.05) compared with mice on control diet. We explored whether tricin may exert its effect via inhibition of cyclooxygenase (COX) enzymes. Its effect on COX activity was assessed in purified enzyme preparations in vitro and its ability to reduce prostaglandin E(2) (PGE(2)) levels in human colon-derived human colon epithelial cell (HCEC) and HCA-7 cells in vitro and in Apc(Min) mice in vivo. Tricin inhibited activity of purified COX-1 and COX-2 enzyme preparations with IC(50) values of approximately 1 micromol/L. At 5 micromol/L, it reduced PGE(2) production in HCEC or HCA-7 cells by 36% (P < 0.01) and 35% (P < 0.05), respectively. COX-2 expression was reduced by tricin weakly in HCEC and unaffected in HCA-7 cells. PGE(2) levels in the small intestinal mucosa and blood of Apc(Min) mice that had received tricin were reduced by 34% (P < 0.01) and 40% (P < 0.05), respectively, compared with control mice. The results suggest that tricin should be further evaluated as a putative colorectal cancer chemopreventive agent.
authors.affiliation: Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Robert Kilpatrick Clinical Sciences Building, UK.
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.forename: Mohammad
authors.initials: M
authors.lastname: Al-Fayez
authors.forename: Richard G
authors.initials: RG
authors.lastname: Tunstall
authors.forename: Sharon
authors.initials: S
authors.lastname: Platton
authors.forename: Peter
authors.initials: P
authors.lastname: Greaves
authors.forename: William P
authors.initials: WP
authors.lastname: Steward
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Gescher
mesh_terms: D000236:Adenoma / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004032:Diet; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use*; D017491:Genes, APC / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012275:Oryza; D014018:Tissue Distribution
chemical_list: D016861:Cyclooxygenase Inhibitors; D005419:Flavonoids; C017769:tricin; D015232:Dinoprostone