Publications
Detailed Information
Nrf2-Keap1 and NF-kB-IkB Kinase Axes as Potential Chemopreventive Targets of Guggulsterone in Human Mammary Epithelial Cells
인체유방상피세포에서 Nrf2-Keap1 및 NF-kB-IkB Kinase를 표적으로 하는 Guggulsterone의 화학 암예방 기전
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Surh, Young-Joon | - |
dc.contributor.author | Inas Saleh Almazari | - |
dc.date.accessioned | 2019-07-02T15:26:32Z | - |
dc.date.available | 2019-07-02T15:26:32Z | - |
dc.date.issued | 2012-02 | - |
dc.identifier.other | 000000002298 | - |
dc.identifier.uri | https://hdl.handle.net/10371/156448 | - |
dc.identifier.uri | http://dcollection.snu.ac.kr:80/jsp/common/DcLoOrgPer.jsp?sItemId=000000002298 | ko_KR |
dc.description.abstract | Guggulsterone (GS) is a phytosterol found in the gum resin of Commiphora mukul. GS has naturally two stereoisomers, E-guggulsterone (cis-GS) and Z-guggulsterone (trans-GS). The anti-inflammatory and antioxidant effects of both GS stereoisomers were explored in human mammary epithelial (MCF10A) cells. cis-GS upregulated the expression of the antioxidant enzyme heme oxygenase-1 (HO-1) to a greater extent than trans-GS in MCF10A cells. cis-GS induced HO-1 expression in dose- and time-dependent manners. NF-E2-related factor (Nrf2) is a basic-leucine zipper transcription factor that plays a key role in regulating the antioxidant/electrophile response element (ARE/EpRE)-mediated expression of various phase-II detoxifying or antioxidant enzymes including HO-1. cis-GS (20 microM) induced the nuclear translocation and ARE/DNA binding activity of Nrf2 in MCF10A cells. In addition, GS pretreatment and co-treatment suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2) in MCF10A cells. Again, cis-GS was more potent than the trans-isomer, which might be due to its greater Nrf2-induced antioxidative activity. TPA-induced NF-kB/DNA binding activity was markedly suppressed by cis-GS co-treatment for 2 h in MCF10A cells in a concentration-dependent manner. In an attempt to investigate the role of Nrf2 activation in the anti-inflammatory effect of GS, expression of both HO-1 and COX-2 induced by cis-GS treatment was examined in cells transfected with Nrf2-siRNA. COX-2 levels were noticeably elevated in Nrf2-knocked down cells upon TPA treatment compared to cells transfected with scrambled siRNA. cis-GS co-treatment inhibited TPA-induced phosphorylation of IκBα and p65 in a concentration dependent manner. Moreover, co-treatment of MCF10A cells with cis-GS (25 µM) for 2 h inhibited the TPA-induced phosphorylation of IKKalpha/beta. These findings suggest that cis-GS by providing the cells with the acquired antioxidant and anti-inflammatory defense capacity, confers protection against carcinogenesis. | - |
dc.format.extent | 136 | - |
dc.language.iso | eng | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject.ddc | 615 | - |
dc.title | Nrf2-Keap1 and NF-kB-IkB Kinase Axes as Potential Chemopreventive Targets of Guggulsterone in Human Mammary Epithelial Cells | - |
dc.type | Thesis | - |
dc.type | Dissertation | - |
dc.contributor.AlternativeAuthor | 알마자리 | - |
dc.description.degree | Doctor | - |
dc.contributor.affiliation | 약학과 | - |
dc.date.awarded | 2012-02 | - |
dc.title.subtitle | 인체유방상피세포에서 Nrf2-Keap1 및 NF-kB-IkB Kinase를 표적으로 하는 Guggulsterone의 화학 암예방 기전 | - |
dc.identifier.holdings | 000000000006▲000000000011▲000000002298▲ | - |
- Appears in Collections:
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.