DC Field | Value | Language |
---|---|---|
dc.contributor.author | D E Lee | - |
dc.contributor.author | K W Lee | - |
dc.contributor.author | S Byun | - |
dc.contributor.author | S K Jung | - |
dc.contributor.author | N Song | - |
dc.contributor.author | S H Lim | - |
dc.contributor.author | Y S Heo | - |
dc.contributor.author | J E Kim | - |
dc.contributor.author | N J Kang | - |
dc.contributor.author | Bo Yeon Kim | - |
dc.contributor.author | G T Bowden | - |
dc.contributor.author | A M Bode | - |
dc.contributor.author | H J Lee | - |
dc.contributor.author | Z Dong | - |
dc.date.accessioned | 2017-04-19T09:22:55Z | - |
dc.date.available | 2017-04-19T09:22:55Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | 10.1074/jbc.M110.147348 | ko |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/10116 | - |
dc.description.abstract | Nonmelanoma 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.publisher | Amer Soc Biochemistry Molecular Biology Inc | - |
dc.title | 7,3',4'-trihydroxyisoflavone, a metabolite of the soy isoflavone Daidzein, suppresses ultraviolet B-induced skin cancer by targeting Cot and MKK4 | - |
dc.title.alternative | 7,3',4'-trihydroxyisoflavone, a metabolite of the soy isoflavone Daidzein, suppresses ultraviolet B-induced skin cancer by targeting Cot and MKK4 | - |
dc.type | Article | - |
dc.citation.title | Journal of Biological Chemistry | - |
dc.citation.number | 16 | - |
dc.citation.endPage | 14256 | - |
dc.citation.startPage | 14246 | - |
dc.citation.volume | 286 | - |
dc.contributor.affiliatedAuthor | Bo Yeon Kim | - |
dc.contributor.alternativeName | 이동은 | - |
dc.contributor.alternativeName | 이기원 | - |
dc.contributor.alternativeName | 변상인 | - |
dc.contributor.alternativeName | 정석근 | - |
dc.contributor.alternativeName | 송누리 | - |
dc.contributor.alternativeName | 임승환 | - |
dc.contributor.alternativeName | 허용석 | - |
dc.contributor.alternativeName | 김종은 | - |
dc.contributor.alternativeName | 강남주 | - |
dc.contributor.alternativeName | 김보연 | - |
dc.contributor.alternativeName | Bowden | - |
dc.contributor.alternativeName | Bode | - |
dc.contributor.alternativeName | 이형주 | - |
dc.contributor.alternativeName | 동지강 | - |
dc.identifier.bibliographicCitation | Journal of Biological Chemistry, vol. 286, no. 16, pp. 14246-14256 | - |
dc.identifier.doi | 10.1074/jbc.M110.147348 | - |
dc.description.journalClass | Y | - |
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