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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 ApcMin 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 E2 (PGE2) levels in human colon–derived human colon epithelial cell (HCEC) and HCA-7 cells in vitro and in ApcMin mice in vivo. Tricin inhibited activity of purified COX-1 and COX-2 enzyme preparations with IC50 values of ∼1 μmol/L. At 5 μmol/L, it reduced PGE2 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. PGE2 levels in the small intestinal mucosa and blood of ApcMin 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.

Dietary modulation of carcinogenesis-related pathwaysDietary item or component studied:tricin, apigenin, querceninPathways studied:COX-catalysed PGE-2 generationStudy type (in vitro, animals, humans): in vitroTissue/biological material/sample size:colorectal cell line HT-29, HCA-7Mode of exposure (if in vivo) (acute, chronic, root of exposure):different time points. KEYWORDS CLASSIFICATION: Animals;Anticarcinogenic Agents;Apigenin;biosynthesis;chemistry;Cell Line,Transformed;Cell Line,Tumor;Cell Proliferation;Cyclooxygenase 1;Cyclooxygenase 2;Cyclooxygenase Inhibitors;dietary modulation of carcinogenesis-related pathways;drug effects;Dinoprostone;Dose-Response Relationship,Drug;Flavonoids;HT29 Cells;Humans;Intramolecular Oxidoreductases;metabolism;Models,Biological;Molecular Structure;Oxidoreductases;pharmacology;Prostaglandin-Endoperoxide Synthases;Quercetin;Research;Sheep;Tetradecanoylphorbol Acetate. OBJECTIVES: Diet-derived flavonoids possess cancer chemopreventive properties in preclinical models. The knowledge of the pharmacology of most flavonoids is insufficient to warrant their advancement to clinical evaluation. METHODS: Here the three flavonoids tricin from rice bran, apigenin from leafy vegetables, and quercetin from onions and apples, were compared in terms of their ability to modulate cyclooxygenase- (COX-) catalyzed prostaglandin E-2 (PGE-2) generation. Specifically their effects on the following parameters were studied: (1) COX enzyme activity, (2) COX-2 expression in human-derived colon cancer cells HCA-7, which express COX-2 constitutively, (3) phorbol ester-mediated COX-2 induction in human colon epithelial cells (HCEC), and (4) PGE-2 levels in cellular incubations. RESULTS: Tricin and quercetin inhibited enzyme activity in purified COX-1 and -2 preparations with IC50 values of near 1 (tricin) and 5 microM (quercetin). Apigenin at up to 25 microM did not affect COX enzyme activity. Flavonoids were incubated with cells for 6 or 24 h and COX-2 protein expression and PGE-2 levels were assessed by Western blot and competitive immunoassay, respectively. None of the agents affected constitutive COX-2 expression in HCA-7 cells. Apigenin, but not tricin or quercetin, down-regulated inducible COX-2 expression in HCEC cells on 6 h incubation. All three flavonoids reduced cellular levels of PGE-2 in the supernatant of HCA-7 cells at both time points and of HCEC cells at 6 h. CONCLUSIONS: The results demonstrate that these structurally similar flavonoids regulate COX-mediated PGE-2 production in different fashions. Their ability to attenuate prostanoid levels may contribute to their cancer chemopreventive efficacy.