7,3',4'-trihydroxyisoflavone, a metabolite of the soy isoflavone Daidzein, suppresses ultraviolet B-induced skin cancer by targeting Cot and MKK4

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dc.contributor.authorD E Lee-
dc.contributor.authorK W Lee-
dc.contributor.authorS Byun-
dc.contributor.authorS K Jung-
dc.contributor.authorN Song-
dc.contributor.authorS H Lim-
dc.contributor.authorY S Heo-
dc.contributor.authorJ E Kim-
dc.contributor.authorN J Kang-
dc.contributor.authorBo Yeon Kim-
dc.contributor.authorG T Bowden-
dc.contributor.authorA M Bode-
dc.contributor.authorH J Lee-
dc.contributor.authorZ Dong-
dc.date.accessioned2017-04-19T09:22:55Z-
dc.date.available2017-04-19T09:22:55Z-
dc.date.issued2011-
dc.identifier.issn0021-9258-
dc.identifier.uri10.1074/jbc.M110.147348ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/10116-
dc.description.abstractNonmelanoma skin cancer is one of the most frequently occurring cancers in the United States. Chronic exposure to UVB irradiation is a major cause of this cancer. Daidzein, along with genistein, is a major isoflavone found in soybeans; however, little is known about the chemopreventive effects of daidzein and its metabolites in UVB-induced skin cancer. Here, we found that 7,3',4'- trihydroxyisoflavone (THIF), a major metabolite of daidzein, effectively inhibits UVB-induced cyclooxygenase 2 (COX-2) expression through the inhibition of NF-kB transcription activity in mouse skin epidermal JB6 P+ cells. In contrast, daidzein had no effect on COX-2 expression levels. Data from Western blot and kinase assays showed that 7,3',4'-THIF inhibited Cot and MKK4 activity, thereby suppressing UVB-induced phosphorylation of mitogen-activated protein kinases. Pull-down assays indicated that 7,3',4'-THIF competed with ATP to inhibit Cot or MKK4 activity. Topical application of 7,3',4'-THIF clearly suppressed the incidence and multiplicity of UVB-induced tumors in hairless mouse skin. Hairless mouse skin results also showed that 7,3',4'-THIF inhibits Cot or MKK4 kinase activity directly, resulting in suppressed UVB-induced COX-2 expression. A docking study revealed that 7,3',4'-THIF, but not daidzein, easily docked to the ATP binding site of Cot and MKK4, which is located between the N-and C-lobes of the kinase domain. Collectively, these results provide insight into the biological actions of 7,3',4'-THIF, a potential skin cancer chemopreventive agent.-
dc.publisherAmer Soc Biochemistry Molecular Biology Inc-
dc.title7,3',4'-trihydroxyisoflavone, a metabolite of the soy isoflavone Daidzein, suppresses ultraviolet B-induced skin cancer by targeting Cot and MKK4-
dc.title.alternative7,3',4'-trihydroxyisoflavone, a metabolite of the soy isoflavone Daidzein, suppresses ultraviolet B-induced skin cancer by targeting Cot and MKK4-
dc.typeArticle-
dc.citation.titleJournal of Biological Chemistry-
dc.citation.number16-
dc.citation.endPage14256-
dc.citation.startPage14246-
dc.citation.volume286-
dc.contributor.affiliatedAuthorBo Yeon Kim-
dc.contributor.alternativeName이동은-
dc.contributor.alternativeName이기원-
dc.contributor.alternativeName변상인-
dc.contributor.alternativeName정석근-
dc.contributor.alternativeName송누리-
dc.contributor.alternativeName임승환-
dc.contributor.alternativeName허용석-
dc.contributor.alternativeName김종은-
dc.contributor.alternativeName강남주-
dc.contributor.alternativeName김보연-
dc.contributor.alternativeNameBowden-
dc.contributor.alternativeNameBode-
dc.contributor.alternativeName이형주-
dc.contributor.alternativeName동지강-
dc.identifier.bibliographicCitationJournal of Biological Chemistry, vol. 286, no. 16, pp. 14246-14256-
dc.identifier.doi10.1074/jbc.M110.147348-
dc.description.journalClassY-
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Ochang Branch Institute > Chemical Biology Research Center > 1. Journal Articles
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