Differential modulation of cyclooxygenase-mediated prostaglandin production by the putative cancer chemopreventive flavonoids tricin, apigenin and quercetin

Alfayez, Mohammad; Cai, Hong; Tunstall, Richard; Steward, William P.; Gescher, Andreas J.

doi:10.1007/s00280-006-0228-3

Cited by 74 publications

(61 citation statements)

References 20 publications

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“…1), which occurs in rice bran and other grass species, and its closely related cogener apigenin (4',5,7-trihydroxyflavone, see Fig. 1) from leafy vegetables were recently shown to interfere effectively with prostaglandin generation in human colorectal cells [3]. 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.…”

Section: Introductionmentioning

confidence: 90%

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: Introductionmentioning

confidence: 90%

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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“…In addition, the results that dietary tricin lowered the ABI of adenocarcinoma cells suggest that tricin affects the chromosomal instability of cancer cells and possibly their telomerase activity (41). Tricin may exert chemopreventive activity through inhibition of COX-1 and 2 enzymes and prostaglandin E 2 production in human colon cancer cell lines (HT-29 and HCA-7) and the small intestine of Apc Min/+ mice (23,24). Unexpectedly, dietary tricin did not significantly alter the expression of COX-2 or iNOS at week 8.…”

Section: Discussionmentioning

confidence: 99%

“…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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“…This has been shown for epicatechingallate, quercetin, resveratrol and genistein in colon cells in vitro. 39,40 In addition to the capacity of AE to modulate detoxification related genes, AE also seemed to modulate several other genes spotted on the custom array that are related to important functions such as, tumor suppression, cell cycle control, cell signaling as well as apoptosis. For instance, AE increased the expression of 5 established or candidate tumor suppressor genes namely, BRCA2, PTPRT, PTPN6, PTPRN and PTPRJ (Dep-1) in LT97 cells.…”

Section: Discussionmentioning

confidence: 99%

Apple polyphenols modulate expression of selected genes related to toxicological defence and stress response in human colon adenoma cells

Selvaraju

Miene

Habermann

et al. 2008

Intl Journal of Cancer

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Apples contain significant amounts of flavonoids that are potentially cancer risk reducing by acting antioxidative or antiproliferative and by favorably modulating gene expression. The purpose of this study was to investigate whether polyphenols from apples modulate expression of genes related to colon cancer prevention in preneoplastic cells derived from colon adenoma (LT97). For this, LT97 cells were treated with effective concentrations of apple extracts (AEs). RNA was isolated and used for synthesis and labeling of cDNA that was hybridized to cDNA-arrays. Gene expression studies were performed using a commercial cDNA-array from Superarray ® that contains a limited number of genes (96 genes) related to drug metabolism, and a custom-made cDNA microarray that contains a higher number of genes (300 genes, including some genes from Superarray) related to mechanisms of carcinogenesis or chemoprevention. Real-time PCR and enzyme activity assays were additionally performed to confirm selected array results. Treatment of cells with AE resulted in 30 and 46 genes expressed over cut-off values ( 1.5-or 0.7-fold) in Superarray and custom array, respectively. Of 87 genes spotted on both arrays, 4 genes (CYP3A7, CYP4F3, CHST7, GSTT2) were regulated with similar directional changes. Expression of selected phase II genes (GSTP1, GSTT2, GSTA4, UGT1A1, UGT2B7), regulated on either array, was confirmed by real-time PCR. The enzyme activities of glutathione S-transferases and UDP-glucuronosyltransferases were altered by treatment of LT97 cells with AE. The observed altered gene expression patterns in LT97 cells, resulting from AE treatment, points to a possible protection of the cells against some toxicological insults.

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Differential modulation of cyclooxygenase-mediated prostaglandin production by the putative cancer chemopreventive flavonoids tricin, apigenin and quercetin

Abstract: 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.

Cited by 74 publications

References 20 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

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

Apple polyphenols modulate expression of selected genes related to toxicological defence and stress response in human colon adenoma cells

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