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Sulforaphane inhibits phorbol ester-stimulated IKK-NF-kappa B signaling and COX-2 expression in human mammary epithelial cells by targeting NF-kappa B activating kinase and ERK
DC Field | Value | Language |
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dc.contributor.author | Kim, Ha-Na | - |
dc.contributor.author | Kim, Do-Hee | - |
dc.contributor.author | Kim, Eun-Hee | - |
dc.contributor.author | Lee, Mee-Hyun | - |
dc.contributor.author | Kundu, Joydeb Kumar | - |
dc.contributor.author | Na, Hye-Kyung | - |
dc.contributor.author | Cha, Young-Nam | - |
dc.contributor.author | Surh, Young-Joon | - |
dc.date.accessioned | 2021-01-31T10:17:24Z | - |
dc.date.available | 2021-01-31T10:17:24Z | - |
dc.date.created | 2017-11-15 | - |
dc.date.issued | 2014-08 | - |
dc.identifier.citation | Cancer Letters, Vol.351 No.1, pp.41-49 | - |
dc.identifier.issn | 0304-3835 | - |
dc.identifier.other | 1248 | - |
dc.identifier.uri | https://hdl.handle.net/10371/172790 | - |
dc.description.abstract | Sulforaphane, an isothiocyanate present in cruciferous vegetables, has been reported to possess anti-inflammatory and cancer chemopreventive properties. However, the molecular mechanisms by which sulforaphane suppresses inflammation and carcinogenesis are yet to be fully elucidated. Since the aberrant expression of cyclooxygenase-2 (COX-2) links inflammation and cancer, the present study was aimed to elucidate the mechanisms by which sulforaphane modulates COX-2 overexpression in human mammary epithelial (MCF-10A) cells stimulated with a prototypic tumor promoter 12-O-tetradecanoylphorbol-beta-acetate (TPA). Treatment of MCF-10A cells with sulforaphane significantly inhibited TPA-induced expression of COX-2 protein and its mRNA transcript. Transient transfection of cells with deletion mutant constructs of COX-2 promoter revealed that the transcription factor nuclear factor-kappaB (NF-kappa B) plays a key role in TPA-induced COX-2 expression in MCF-10A cells. Pretreatment with sulforaphane significantly attenuated nuclear localization, DNA binding and the transcriptional activity of NF-kappa B through inhibition of phosphorylation and subsequent degradation of I kappa B alpha in MCF-10A cells stimulated with TPA. Sulforaphane also attenuated TPA-induced activation of I kappa B kinases (IKK), NF-kappa B-activating kinase (NAK) and extracellular signal-regulated kinase-1/2 (ERK1/2). Pharmacological inhibition of IKK or transient transfection of cells with dominant-negative mutant forms of this kinase abrogated TPA-induced NF-kappa B activation and COX-2 expression. In addition, the blockade of ERK1/2 activation negated the catalytic activity of IKK alpha, but not that of IKK beta, whereas silencing NAK by specific siRNA abrogated the IKK beta activity in TPA-treated cells. Taken together, sulforaphane inhibits TPA-induced NF-kappa B activation and COX-2 expression in MCF-10A cells by blocking two distinct signaling pathways mediated by ERK1/2-IKK alpha and NAK-IKK beta. (C) 2014 Elsevier Ireland Ltd. All rights reserved. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier BV | - |
dc.title | Sulforaphane inhibits phorbol ester-stimulated IKK-NF-kappa B signaling and COX-2 expression in human mammary epithelial cells by targeting NF-kappa B activating kinase and ERK | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 서영준 | - |
dc.identifier.doi | 10.1016/j.canlet.2014.03.037 | - |
dc.citation.journaltitle | Cancer Letters | - |
dc.identifier.wosid | 000339775300006 | - |
dc.identifier.scopusid | 2-s2.0-84903698145 | - |
dc.citation.endpage | 49 | - |
dc.citation.number | 1 | - |
dc.citation.startpage | 41 | - |
dc.citation.volume | 351 | - |
dc.identifier.sci | 000339775300006 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Surh, Young-Joon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | PROSTAGLANDIN-ENDOPEROXIDE SYNTHASE-2 | - |
dc.subject.keywordPlus | INDUCED CYCLOOXYGENASE-2 EXPRESSION | - |
dc.subject.keywordPlus | POTENTIAL MOLECULAR TARGETS | - |
dc.subject.keywordPlus | NUCLEAR-FACTOR | - |
dc.subject.keywordPlus | MOUSE SKIN | - |
dc.subject.keywordPlus | CHEMOPREVENTIVE AGENT | - |
dc.subject.keywordPlus | TRANSCRIPTIONAL REGULATION | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | P65 SUBUNIT | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordAuthor | Sulforaphane | - |
dc.subject.keywordAuthor | Cyclooxygenase-2 | - |
dc.subject.keywordAuthor | NF-kappa B-activating kinase | - |
dc.subject.keywordAuthor | IkappaB kinase | - |
dc.subject.keywordAuthor | Chemoprevention | - |
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