title: (-)-Epigallocatechin-3-gallate blocks nicotine-induced matrix metalloproteinase-9 expression and invasiveness via suppression of NF-κB and AP-1 in endothelial cells.
abstract: Cigarette smoke, specifically the nicotine contained within, has been shown to correlate closely with cell invasion and strategies to downregulate their expression may ultimately be of clinical utility. Matrix metalloproteinase-9 (MMP-9) is critically involved in the cell invasion and metastasis processes. Since nicotine plays a crucial role in the regulation of MMP-9 expression, the investigation of plant-derived compounds capable of modulating nicotine-induced signaling is an issue of concern. In this study, the effects of (-)-epigallocatechin-3-gallate (EGCG), a major green tea catechin, on nicotine-induced cell invasion and MMP-9 activity in ECV304 human endothelial cells were examined. EGCG treatment was found to reduce the MMP-9 expression and transcriptional activity in a dose-dependent manner. EGCG inhibited nicotine-activated production of reactive oxygen species (ROS), which are known as important signaling molecules to activate MMP-9. To further study the mechanisms for the EGCG-mediated regulation of MMP-9, the transcription factors NF-κB and AP-1 activities were examined. EGCG suppressed the nicotine-induced NF-κB and AP-1 activation. Studies with expression vectors encoding mutated NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the nicotine-stimulated MMP-9 expression. EGCG also abrogated the nicotine-induced activation of AP-1 subunits c-fos and c-jun. The above studies demonstrate that EGCG may exert at least part of its anti-invasive effect in ECV304 human endothelial cells by controlling MMP-9 expression through the suppression of ROS, NF-κB and AP-1.
authors.affiliation: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Republic of Korea.
authors.forename: Pham Ngoc
authors.initials: PN
authors.lastname: Khoi
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Park
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Yong
authors.initials: Y
authors.lastname: Xia
authors.forename: Nam Ho
authors.initials: NH
authors.lastname: Kim
authors.forename: Kyung Keun
authors.initials: KK
authors.lastname: Kim
authors.forename: Young Do
authors.initials: YD
authors.lastname: Jung
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009538:Nicotine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D009538:Nicotine; D002392:Catechin; C045651:epigallocatechin gallate; D020780:Matrix Metalloproteinase 9