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dc.contributor.authorVauzour, David
dc.contributor.authorVafeiadou, Katerina
dc.contributor.authorRice-Evans, Catherine
dc.contributor.authorCadenas, Enrique
dc.contributor.authorSpencer, Jeremy P. E.
dc.identifier.citationVauzour , D , Vafeiadou , K , Rice-Evans , C , Cadenas , E & Spencer , J P E 2007 , ' Inhibition of cellular proliferation by the genistein metabolite 5,7,3',4'-tetrahydroxyisoflavone is mediated by DNA damage and activation of the ATR signalling pathway ' , Archives of Biochemistry and Biophysics , vol. 468 , no. 2 , pp. 159-66 .
dc.identifier.otherPURE: 2234291
dc.identifier.otherPURE UUID: 6e7d85c4-1b8c-44f1-983c-267587d1169b
dc.identifier.otherPubMed: 17976513
dc.identifier.otherScopus: 36148974705
dc.description.abstractThe cellular actions of genistein, and its in vivo metabolites, are believed to mediate the decreased risk of breast cancer associated with high soy consumption. The genistein metabolite, 5,7,3',4'-tetrahydroxyisoflavone (THIF), induced G2-M cell cycle arrest in T47D tumorigenic breast epithelial cells via a mechanism involving the activation of ataxia telangiectasia and Rad3-related kinase (ATR) via its phosphorylation at Ser428. This activation of ATR appeared to result from THIF-induced increases in intracellular oxidative stress, a depletion of cellular GSH and an increase in DNA strand breakage. THIF treatment also led to an inhibition of cdc2, which was accompanied by the phosphorylation of both p53 (Ser15) and Chk1 (Ser296) and the de-activation of cdc25C phosphatase. We suggest the anti-proliferative actions of THIF may be mediated by initial oxidative DNA damage, activation of ATR and downstream regulation of the p53 and Chk1 pathways leading to cell cycle arrest in G2-M. This may represent one mechanism by which genistein exerts its cellular activity in vivo.en
dc.relation.ispartofArchives of Biochemistry and Biophysics
dc.subjectBreast Neoplasms
dc.subjectCell Cycle Proteins
dc.subjectCell Line, Tumor
dc.subjectCell Proliferation
dc.subjectDNA Damage
dc.subjectDose-Response Relationship, Drug
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectSignal Transduction
dc.titleInhibition of cellular proliferation by the genistein metabolite 5,7,3',4'-tetrahydroxyisoflavone is mediated by DNA damage and activation of the ATR signalling pathwayen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionAgriculture, Veterinary and Food Sciences
dc.contributor.institutionNutrition and Dietetics
dc.contributor.institutionDepartment of Human and Environmental Sciences
dc.description.statusPeer reviewed
rioxxterms.typeJournal Article/Review

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