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Guggulsterone induces heme oxygenase-1 expression through activation of Nrf2 in human mammary epithelial cells: PTEN as a putative target
DC Field | Value | Language |
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dc.contributor.author | Almazari, Inas | - |
dc.contributor.author | Park, Jong-Min | - |
dc.contributor.author | Park, Sin-Aye | - |
dc.contributor.author | Suh, Jin-Young | - |
dc.contributor.author | Na, Hye-Kyung | - |
dc.contributor.author | Cha, Young-Nam | - |
dc.contributor.author | Surh, Young-Joon | - |
dc.date.accessioned | 2021-01-31T09:28:36Z | - |
dc.date.available | 2021-01-31T09:28:36Z | - |
dc.date.created | 2017-11-15 | - |
dc.date.issued | 2012-02 | - |
dc.identifier.citation | Carcinogenesis, Vol.33 No.2, pp.368-376 | - |
dc.identifier.issn | 0143-3334 | - |
dc.identifier.other | 2078 | - |
dc.identifier.uri | https://hdl.handle.net/10371/172710 | - |
dc.description.abstract | Guggulsterone (GS) [4,17(20)-pregnadiene-3,16-dione] is a phytosterol found in the gum resin of the Commiphora mukul. GS exists naturally in two stereoisomers: E-GS (cis-GS) and Z-GS (trans-GS). In this study, the effects of both isomers on expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) were evaluated in human mammary epithelial (MCF10A) cells. NF-E2-related factor 2 (Nrf2) is considered a master regulator in activating antioxidant response element (ARE)-driven expression of HO-1 and many other antioxidant/cytoprotective proteins. cis-GS upregulated the transcription and protein expression of HO-1 to a greater extent than did trans-GS. cis-GS treatment enhanced nuclear translocation and ARE-binding activity of Nrf2. MCF10A cells transfected with an ARE luciferase construct exhibited significantly elevated Nrf2 transcriptional activity upon cis-GS treatment compared with cells transfected with the control vector. In addition, silencing of the Nrf2 gene abrogated cis-GS-induced expression of HO-1. Incubation of MCF10A cells with cis-GS increased phosphorylation of Akt. The pharmacological inhibition of phosphoinositide 3-kinase (PI3K), an upstream kinase responsible for Akt phosphorylation, abrogated cis-GS-induced Nrf2 nuclear translocation. Pretreatment with the thiol-reducing agents attenuated Akt phosphorylation, Nrf2 activation and HO-1 expression, suggesting that cis-GS may cause thiol modification of an upstream signaling modulator. Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN) is a negative regulator of the PI3K-Akt axis. The mutation in cysteine 124 present in the catalytic domain of PTEN abolished cis-GS-induced HO-1 expression as well as Akt phosphorylation. Whether this cysteine is a 'bona fide' target of cis-GS in its activation of Nrf2 needs additional investigation. | - |
dc.language | 영어 | - |
dc.publisher | Oxford University Press | - |
dc.title | Guggulsterone induces heme oxygenase-1 expression through activation of Nrf2 in human mammary epithelial cells: PTEN as a putative target | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 서영준 | - |
dc.identifier.doi | 10.1093/carcin/bgr259 | - |
dc.citation.journaltitle | Carcinogenesis | - |
dc.identifier.wosid | 000300039800018 | - |
dc.identifier.scopusid | 2-s2.0-84863027990 | - |
dc.citation.endpage | 376 | - |
dc.citation.number | 2 | - |
dc.citation.startpage | 368 | - |
dc.citation.volume | 33 | - |
dc.identifier.sci | 000300039800018 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Surh, Young-Joon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | SIGNALING PATHWAY | - |
dc.subject.keywordPlus | TUMOR SUPPRESSION | - |
dc.subject.keywordPlus | OXIDATIVE STRESS | - |
dc.subject.keywordPlus | REDOX REGULATION | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | PHOSPHATASE | - |
dc.subject.keywordPlus | INDUCTION | - |
dc.subject.keywordPlus | KINASE | - |
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