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

2.50
Hdl Handle:
http://hdl.handle.net/10146/54433
Title:
Differential modulation of cyclooxygenase-mediated prostaglandin production by the putative cancer chemopreventive flavonoids tricin, apigenin and quercetin.
Authors:
Al-Fayez, Mohammad; Cai, Hong; Tunstall, Richard; Steward, William P.; Gescher, Andreas J.
Abstract:
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.
Citation:
Cancer Chemother. Pharmacol. 2006, 58 (6):816-825
Journal:
Cancer chemotherapy and pharmacology
Issue Date:
Dec-2006
URI:
http://hdl.handle.net/10146/54433
DOI:
10.1007/s00280-006-0228-3
PubMed ID:
16552572
Additional Links:
http://www.springerlink.com/content/2q138j35r5776141/
Type:
Article
Language:
en
Description:
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.
ISSN:
0344-5704
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorAl-Fayez, Mohammad-
dc.contributor.authorCai, Hong-
dc.contributor.authorTunstall, Richard-
dc.contributor.authorSteward, William P.-
dc.contributor.authorGescher, Andreas J.-
dc.date.accessioned2009-03-12T09:06:15Z-
dc.date.available2009-03-12T09:06:15Z-
dc.date.issued2006-12-
dc.identifier.citationCancer Chemother. Pharmacol. 2006, 58 (6):816-825en
dc.identifier.issn0344-5704-
dc.identifier.pmid16552572-
dc.identifier.doi10.1007/s00280-006-0228-3-
dc.identifier.urihttp://hdl.handle.net/10146/54433-
dc.descriptionDietary 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.en
dc.description.abstractOBJECTIVES: 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.en
dc.language.isoenen
dc.relation.urlhttp://www.springerlink.com/content/2q138j35r5776141/en
dc.subjectCancer chemopreventionen
dc.subjectFlavonoidsen
dc.subjectCyclooxygenaseen
dc.subjectProstaglandin E-2en
dc.subject.meshAnimals-
dc.subject.meshAnticarcinogenic Agents-
dc.subject.meshApigenin-
dc.subject.meshCell Line, Transformed-
dc.subject.meshCell Line, Tumor-
dc.subject.meshCell Proliferation-
dc.subject.meshCyclooxygenase 1-
dc.subject.meshCyclooxygenase 2-
dc.subject.meshCyclooxygenase Inhibitors-
dc.subject.meshDinoprostone-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshFlavonoids-
dc.subject.meshHT29 Cells-
dc.subject.meshHumans-
dc.subject.meshIntramolecular Oxidoreductases-
dc.subject.meshModels, Biological-
dc.subject.meshMolecular Structure-
dc.subject.meshProstaglandin-Endoperoxide Synthases-
dc.subject.meshQuercetin-
dc.subject.meshSheep-
dc.subject.meshTetradecanoylphorbol Acetate-
dc.titleDifferential modulation of cyclooxygenase-mediated prostaglandin production by the putative cancer chemopreventive flavonoids tricin, apigenin and quercetin.en
dc.typeArticleen
dc.identifier.journalCancer chemotherapy and pharmacologyen

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