期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 43, 期 3, 页码 868-876出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2013.2006
关键词
EGCG; nicotine; MMP-9; ROS; NF-kappa B; AP-1; cell invasion
类别
资金
- National Cancer Center [0720570]
- National Research Foundation of Korea (NRF) [2010-0009910]
- National Research Foundation of Korea (NRF) (MRC for Gene Regulation) [2011-0030132]
- Korea government (MSIP)
- National Research Foundation of Korea [2010-0009910, 2011-0030132] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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-kappa B and AP-1 activities were examined. EGCG suppressed the nicotine-induced NF-kappa B and AP-1 activation. Studies with expression vectors encoding mutated NF-kappa B signaling molecules and AP-1 decoy confirmed that NF-kappa B 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-kappa B and AP-1.
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