The reaction of flavanols with nitrous acid protects against N-nitrosamine formation and leads to the formation of nitroso derivatives which inhibit cancer cell growth.

2.50
Hdl Handle:
http://hdl.handle.net/10146/68755
Title:
The reaction of flavanols with nitrous acid protects against N-nitrosamine formation and leads to the formation of nitroso derivatives which inhibit cancer cell growth.
Authors:
Lee, Stephanie Y. H.; Munerol, Bibiana; Pollard, Susan; Youdim, Kuresh A.; Pannala, Ananth S.; Kuhnle, Gunter G. C.; Debnam, Edward S.; Rice-Evans, Catherine; Spencer, Jeremy P. E.
Abstract:
Studies have suggested that diets rich in polyphenols such as flavonoids may lead to a reduced risk of gastrointestinal cancers. We demonstrate the ability of monomeric and dimeric flavanols to scavenge reactive nitrogen species derived from nitrous acid. Both epicatechin and dimer B2 (epicatechin dimer) inhibited nitrous acid-induced formation of 3-nitrotyrosine and the formation of the carcinogenic N-nitrosamine, N-nitrosodimethylamine. The reaction of monomeric and dimeric epicatechin with nitrous acid led to the formation of mono- and di-nitroso flavanols, whereas the reaction with hesperetin resulted primarily in the formation of nitrated products. Although, epicatechin was transferred across the jejunum of the small intestine yielding metabolites, its nitroso form was not absorbed. Dimer B2 but not epicatechin monomer inhibited the proliferation of, and triggered apoptosis in, Caco-2 cells. The latter was accompanied by caspase-3 activation and reductions in Akt phosphorylation, suggesting activation of apoptosis via inhibition of prosurvival signaling. Furthermore, the dinitroso derivative of dimer B2, and to a lesser extent the dinitroso-epicatechin, also induced significant toxic effects in Caco-2 cells. The inhibitory effects on cellular proliferation were paralleled by early inhibition of ERK 1/2 phosphorylation and later reductions in cyclin D1 levels, indicating modulation of cell cycle regulation in Caco-2 cells. These effects highlight multiple routes in which dietary derived flavanols may exert beneficial effects in the gastrointestinal tract.
Citation:
Free Radic. Biol. Med. 2006, 40 (2):323-334
Journal:
Free radical biology & medicine
Issue Date:
15-Jan-2006
URI:
http://hdl.handle.net/10146/68755
DOI:
10.1016/j.freeradbiomed.2005.08.031
PubMed ID:
16413414
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4H9GP12-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=8321c98f33e2dc1be806a3a04a31e30e
Type:
Article
Language:
en
Description:
KEYWORDS - CLASSIFICATION: analogs & derivatives;antagonists & inhibitors;Absorption;Animals;Apoptosis;chemistry;Caco-2 Cells;Caspase 3;Caspases;Catechin;Cell Cycle;Cell Proliferation;Colonic Neoplasms;Cyclin D1;drug effects;drug therapy;dietary modulation of carcinogenesis-related pathways;Dose-Response Relationship,Drug;Drug Screening Assays,Antitumor;Flavonoids;Gastrointestinal Tract;Humans;metabolism;Mitogen-Activated Protein Kinase Kinases;Nitrogen;Nitrosamines;Nitroso Compounds;Nitrous Acid;pharmacology;physiology;Phenols;Phosphorylation;Proteins;Proto-Oncogene Proteins;Proto-Oncogene Proteins c-akt;Rats;Reactive Nitrogen Species;Research;Time Factors;Tyrosine.
ISSN:
0891-5849
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorLee, Stephanie Y. H.-
dc.contributor.authorMunerol, Bibiana-
dc.contributor.authorPollard, Susan-
dc.contributor.authorYoudim, Kuresh A.-
dc.contributor.authorPannala, Ananth S.-
dc.contributor.authorKuhnle, Gunter G. C.-
dc.contributor.authorDebnam, Edward S.-
dc.contributor.authorRice-Evans, Catherine-
dc.contributor.authorSpencer, Jeremy P. E.-
dc.date.accessioned2009-05-22T09:06:04Z-
dc.date.available2009-05-22T09:06:04Z-
dc.date.issued2006-01-15-
dc.identifier.citationFree Radic. Biol. Med. 2006, 40 (2):323-334en
dc.identifier.issn0891-5849-
dc.identifier.pmid16413414-
dc.identifier.doi10.1016/j.freeradbiomed.2005.08.031-
dc.identifier.urihttp://hdl.handle.net/10146/68755-
dc.descriptionKEYWORDS - CLASSIFICATION: analogs & derivatives;antagonists & inhibitors;Absorption;Animals;Apoptosis;chemistry;Caco-2 Cells;Caspase 3;Caspases;Catechin;Cell Cycle;Cell Proliferation;Colonic Neoplasms;Cyclin D1;drug effects;drug therapy;dietary modulation of carcinogenesis-related pathways;Dose-Response Relationship,Drug;Drug Screening Assays,Antitumor;Flavonoids;Gastrointestinal Tract;Humans;metabolism;Mitogen-Activated Protein Kinase Kinases;Nitrogen;Nitrosamines;Nitroso Compounds;Nitrous Acid;pharmacology;physiology;Phenols;Phosphorylation;Proteins;Proto-Oncogene Proteins;Proto-Oncogene Proteins c-akt;Rats;Reactive Nitrogen Species;Research;Time Factors;Tyrosine.en
dc.description.abstractStudies have suggested that diets rich in polyphenols such as flavonoids may lead to a reduced risk of gastrointestinal cancers. We demonstrate the ability of monomeric and dimeric flavanols to scavenge reactive nitrogen species derived from nitrous acid. Both epicatechin and dimer B2 (epicatechin dimer) inhibited nitrous acid-induced formation of 3-nitrotyrosine and the formation of the carcinogenic N-nitrosamine, N-nitrosodimethylamine. The reaction of monomeric and dimeric epicatechin with nitrous acid led to the formation of mono- and di-nitroso flavanols, whereas the reaction with hesperetin resulted primarily in the formation of nitrated products. Although, epicatechin was transferred across the jejunum of the small intestine yielding metabolites, its nitroso form was not absorbed. Dimer B2 but not epicatechin monomer inhibited the proliferation of, and triggered apoptosis in, Caco-2 cells. The latter was accompanied by caspase-3 activation and reductions in Akt phosphorylation, suggesting activation of apoptosis via inhibition of prosurvival signaling. Furthermore, the dinitroso derivative of dimer B2, and to a lesser extent the dinitroso-epicatechin, also induced significant toxic effects in Caco-2 cells. The inhibitory effects on cellular proliferation were paralleled by early inhibition of ERK 1/2 phosphorylation and later reductions in cyclin D1 levels, indicating modulation of cell cycle regulation in Caco-2 cells. These effects highlight multiple routes in which dietary derived flavanols may exert beneficial effects in the gastrointestinal tract.en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4H9GP12-2&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=8321c98f33e2dc1be806a3a04a31e30een
dc.subjectFlavonoiden
dc.subjectEpicatechinen
dc.subjectDimeren
dc.subjectNitriteen
dc.subjectCanceren
dc.subjectN-nitrosationen
dc.subjectFree radicalsen
dc.subject.meshAbsorption-
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshCaco-2 Cells-
dc.subject.meshCaspase 3-
dc.subject.meshCaspases-
dc.subject.meshCatechin-
dc.subject.meshCell Cycle-
dc.subject.meshCell Proliferation-
dc.subject.meshColonic Neoplasms-
dc.subject.meshCyclin D1-
dc.subject.meshDimethylnitrosamine-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshDrug Screening Assays, Antitumor-
dc.subject.meshFlavonoids-
dc.subject.meshGastrointestinal Tract-
dc.subject.meshHumans-
dc.subject.meshMitogen-Activated Protein Kinase Kinases-
dc.subject.meshNitrosamines-
dc.subject.meshNitroso Compounds-
dc.subject.meshNitrous Acid-
dc.subject.meshPhenols-
dc.subject.meshPhosphorylation-
dc.subject.meshProto-Oncogene Proteins c-akt-
dc.subject.meshRats-
dc.subject.meshReactive Nitrogen Species-
dc.subject.meshTime Factors-
dc.subject.meshTyrosine-
dc.titleThe reaction of flavanols with nitrous acid protects against N-nitrosamine formation and leads to the formation of nitroso derivatives which inhibit cancer cell growth.en
dc.typeArticleen
dc.identifier.journalFree radical biology & medicineen
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