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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

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dc.contributor.authorKim, Ha-Na-
dc.contributor.authorKim, Do-Hee-
dc.contributor.authorKim, Eun-Hee-
dc.contributor.authorLee, Mee-Hyun-
dc.contributor.authorKundu, Joydeb Kumar-
dc.contributor.authorNa, Hye-Kyung-
dc.contributor.authorCha, Young-Nam-
dc.contributor.authorSurh, Young-Joon-
dc.date.accessioned2021-01-31T10:17:24Z-
dc.date.available2021-01-31T10:17:24Z-
dc.date.issued2014-08-
dc.identifier.citationCancer Letters, Vol.351 No.1, pp.41-49-
dc.identifier.issn0304-3835-
dc.identifier.other1248-
dc.identifier.urihttps://hdl.handle.net/10371/172790-
dc.description.abstractSulforaphane, 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.subjectSulforaphane-
dc.subjectCyclooxygenase-2-
dc.subjectNF-kappa B-activating kinase-
dc.subjectIkappaB kinase-
dc.subjectChemoprevention-
dc.titleSulforaphane 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.typeArticle-
dc.contributor.AlternativeAuthor서영준-
dc.identifier.doi10.1016/j.canlet.2014.03.037-
dc.citation.journaltitleCancer Letters-
dc.identifier.scopusid2-s2.0-84903698145-
dc.citation.endpage49-
dc.citation.number1-
dc.citation.startpage41-
dc.citation.volume351-
dc.identifier.rimsid1248-
dc.identifier.sci000339775300006-
dc.contributor.affiliatedAuthorSurh, Young-Joon-
Appears in Collections:
Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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