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 f1 Mmol/L. At 5 Mmol/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. [Mol Cancer Ther 2005;4(9):1287-92]

Tissue distribution in mice and metabolism in murine and human liver of apigenin and tricin, flavones with putative cancer chemopreventive properties

“…These methoxy groups may have somewhat hindered the interaction of the tricin molecule with glucuronyl transferase. Levels of tricin exceeded those of apigenin also in the small intestinal tract, and it remains to be seen, whether apigenin will accordingly be less efficacious than tricin in the Apc Min mouse model, in which tricin interfered significantly with small intestinal adenoma development [4]. Flavone metabolites could not be detected in the plasma or liver or gastro-intestinal tissues of mice, which had received dietary flavones, whilst preliminary inspection of the urine of mice exposed to flavones suggests the presence of three conjugate metabolites for apigenin and two for tricin (results not shown).…”

“…Dietary administration is customarily used in rodent intervention studies. The choice of dose was based on the fact that tricin at this dose reduced adenoma multiplicity in the Apc Min mouse [4]. After 5, 6 or 7 days, mice were killed by cardiac exsanguinations under terminal anaesthesia (halothane), and blood was collected.…”

“…This paper suggests that the two flavones exert an effect on prostaglandin production via differential mechanisms, tricin by inhibition of cyclooxygenase (COX) enzyme activity, and apigenin by downregulation of COX-2 expression. Tricin interfered with carcinogenesis in Apc Min mice [4] and C3(1)/SV40 T/t-antigen transgenic ("TAg") mice (Cai, Steward and Gescher, unpublished), genetic models of human carcinogenesis, the former of gastrointestinal origin characterized by an Apc gene mutation, the latter of mammary origin associated with dysfunctional Rb and p53 tumor suppressors. Apigenin remains to be tested in these models.…”

CYP93G2 Is a Flavanone 2-Hydroxylase Required for C-Glycosylflavone Biosynthesis in Rice

“…On the other hand, tricin has in vitro antiproliferative activities on breast and colon cancer cell lines at submicromolar concentrations (Hudson et al, 2000). It effectively inhibits cyclooxygenase enzymes and interferes with murine gastrointestinal carcinogenesis (Cai et al, 2005). However, the preferred consumed form, white rice, consists exclusively of endosperm tissue, which is poor in phytochemicals.…”

Dietary Tricin Suppresses Inflammation-Related Colon Carcinogenesis in Male Crj: CD-1 Mice

“…There are few reports on the effects of dietary tricin on intestinal carcinogenesis. Cai et al (23) reported that feeding a diet containing 0.2% tricin decreased the size and the number of intestinal adenoma formed in Apc Min/+ mice through the inhibition of cyclooxygenase (COX)-2 (23,24). Dietary tricin did not affect tumor formation in the large bowel (23).…”