The rice bran constituent tricin potently inhibits cyclooxygenase enzymes and interferes with intestinal carcinogenesis in <i>ApcMin</i> mice

Cai, Hong; Alfayez, Mohammad; Tunstall, Richard; Platton, Sharon L.; Greaves, Peter; Steward, William P.; Gescher, Andreas J.

doi:10.1158/1535-7163.mct-05-0165

Cited by 98 publications

(81 citation statements)

References 17 publications

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Animals and Treatmentsmentioning

confidence: 99%

“…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with carcinogenesis in Apc Min mice [4] and C3(1)/SV40 T/t-antigen transgenic ("TAg") mice (Cai, Steward and Gescher, unpublished), genetic models of human carcinogenesis, the former of gastrointestinal origin characterized by an Apc gene mutation, the latter of mammary origin associated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.…”

Section: Introductionmentioning

confidence: 99%

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

Cai

Boocock

Steward

et al. 2006

Cancer Chemother Pharmacol

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Purpose: The flavones apigenin and tricin, which occur in leafy vegetables and rice bran, respectively, possess cancer chemopreventive properties in preclinical rodent models. Their pharmacology is only poorly understood. We compared their tissue levels in mice in vivo and their metabolism in liver fractions in vitro. Methods: Mice received apigenin or tricin (0.2%) with their diet for 5-7 days, and flavone levels were compared in the plasma, liver and gastrointestinal mucosa using HPLC-UV. Flavone metabolism was investigated in murine and human liver microsomes or cytosol in vitro co-incubated with uridine 5'-diphosphoglucuronic acid or 3'-phosphoadenosine-5' phosphosulfate. Flavone metabolites were characterized by on-line HPLCmass spectrometry. Results: After dietary administration of flavones for 7 days, levels of tricin in plasma, liver and mucosa exceeded those of apigenin by 350, 33 and 100 %, respectively.Apigenin was more rapidly glucuronidated than tricin in liver microsomes, whilst tricin underwent swifter sulfonation than apigenin in liver cytosol. For either flavone the rate of glucuronidation was much faster than that of sulfonation. Flavone monoglucuronides and monosulfates were identified as metabolites in microsomal and cytosolic incubations, respectively. Conclusions:When consumed with the diet in mice tricin seems to be more available than apigenin in blood and tissues. Differences in their glucuronidation may account for their differential availability. Thus tricin may have a pharmacokinetic advantage over apigenin. This type of information may help decide which flavonoids to select for clinical development.

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Section: Discussionmentioning

confidence: 99%

Section: Animals and Treatmentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Cai

Boocock

Steward

et al. 2006

Cancer Chemother Pharmacol

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“…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.…”

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confidence: 99%

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

et al. 2010

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C-Glycosylflavones are ubiquitous in the plant kingdom, and many of them have beneficial effects on human health. They are a special group of flavonoid glycosides in which the sugars are C-linked to the flavone skeleton. It has been long presumed that C-glycosylflavones have a different biosynthetic origin from O-glycosylflavonoids. In rice (Oryza sativa), a C-glucosyltransferase (OsCGT) that accepts 2-hydroxyflavanone substrates and a dehydratase activity that selectively converts C-glucosyl-2-hydroxyflavanones to 6C-glucosylflavones were recently described. In this study, we provide in vitro and in planta evidence that the rice P450 CYP93G2 protein encoded by Os06g01250 is a functional flavanone 2-hydroxylase. CYP93G2 is related to the CYP93B subfamily, which consists of dicot flavone synthase II enzymes. In the presence of NADPH, recombinant CYP93G2 converts naringenin and eriodictyol to the corresponding 2-hydroxyflavanones. In addition, CYP93G2 generates 2-hydroxyflavanones, which are modified by O-glycosylation in transgenic Arabidopsis (Arabidopsis thaliana). Coexpression of CYP93G2 and OsCGT in Arabidopsis resulted in the production of C-glucosyl-2-hydroxyflavanones in the dibenzoylmethane tautomeric form. The same structure was reported previously for the in vitro OsCGT reaction products. Thus, CYP93G2 generates 2-hydroxyflavanone substrates from flavanones for C-glucosylation by OsCGT in planta. Furthermore, knocking down Os06g01250 in rice (O. sativa subsp. japonica 'Zhonghua 11') preferentially depleted the accumulation of C-glycosylapigenin, C-glycosylluteolin, and C-glycosylchrysoeriol but did not affect the levels of tricin, which is frequently present as O-glycosides in cereals. Taken together, our work conclusively assigned CYP93G2 as the first enzyme that channels flavanones to C-glycosylflavone biosynthesis in rice.

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“…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).…”

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confidence: 99%

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

Oyama

Yasui

Sugie

et al. 2009

Cancer Prevention Research

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The flavone 4′,5,7-trihydroxy-3′,5′-dimethoxyflavone (tricin) present in rice, oats, barley, and wheat exhibits antigrowth activity in several human cancer cell lines and anti-inflammatory potential. However, the chemopreventive activity has not yet been elucidated in preclinical animal models of colorectal cancer. This study was designed to determine whether dietary tricin exerts inflammation-associated colon carcinogenesis induced by azoxymethane and dextran sulfate sodium in mice. Male Crj: CD-1 mice were initiated with a single i.p. injection of azoxymethane (10 mg/kg body weight) and followed by a 1-week exposure to dextran sulfate sodium (1.5%, w/v) in drinking water to induce colonic neoplasms. They were then given the experimental diet containing 50 or 250 ppm tricin. The experiment was terminated at week 18 to determine the chemopreventive efficacy of tricin. In addition, the effects of dietary tricin on the expression of several inflammatory cytokines, including tumor necrosis factor (TNF)-α, were assayed. The development of colonic adenomas and adenocarcinomas was significantly reduced by feeding with 50 and 250 ppm tricin, respectively. Dietary tricin also significantly reduced the proliferation of adenocarcinoma cells as well as the numbers of mitoses/ anaphase bridging in adenocarcinoma cells. The dietary administration with tricin significantly inhibited the expression of TNF-α in the nonlesional cypts. Our findings that dietary tricin inhibits inflammation-related mouse colon carcinogenesis by suppressing the expression of TNF-α in the nonlesional cyrpts and the proliferation of adenocarcinomas suggest a potential use of tricin for clinical trials of colorectal cancer chemoprevention.

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The rice bran constituent tricin potently inhibits cyclooxygenase enzymes and interferes with intestinal carcinogenesis in ApcMin mice

Cited by 98 publications

References 17 publications

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

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

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

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

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