https://scholars.lib.ntu.edu.tw/handle/123456789/570626
Title: | Stimulation of MMP-9 of oral epithelial cells by areca nut extract is related to TGF-ß/Smad2-dependent and -independent pathways and prevented by betel leaf extract, hydroxychavicol and melatonin | Authors: | Chang M.-C. Pan Y.-H. Wu H.-L. Lu Y.-J. Liao W.-C. Yeh C.-Y. JANG-JAER LEE JIIANG-HUEI JENG |
Keywords: | Areca nut; Betel leaf; Hydroxychavicol; MMP-9; Oral cancer | Issue Date: | 2019 | Publisher: | Impact Journals LLC | Journal Volume: | 11 | Journal Issue: | 23 | Start page/Pages: | 11624-11639 | Source: | Aging | Abstract: | Background: There are 200-600 million betel quid (BQ) chewers in the world. BQ increases oral cancer risk. Matrix metalloproteinase-9 (MMP-9) is responsible for matrix degradation, cancer invasion and metastasis. Whether areca nut extract (ANE), a BQ component, stimulates MMP-9 secretion, and the related signaling pathways awaits investigation. Results: ANE (but not arecoline) stimulated MMP-9 production of gingival keratinocytes and SAS cancer epithelial cells. ANE stimulated TGF-?1, p-Smad2, and p-TAK1 protein expression. ANE-induced MMP-9 production/expression in SAS cells can be attenuated by SB431542 (ALK5/Smad2 inhibitor), 5Z-7-Oxozeaenol (TAK1 inhibitor), catalase, PD153035 (EGFR tyrosine kinase inhibitor), AG490 (JAK inhibitor), U0126 (MEK/ERK inhibitor), LY294002 (PI3K/Akt inhibitor), betel leaf (PBL) extract, and hydroxychavicol (HC, a PBL component), and melatonin, but not by aspirin. Conclusions: AN components contribute to oral carcinogenesis by stimulating MMP-9 secretion, thus enhancing tumor invasion/metastasis. These events are related to reactive oxygen species, TGF-?1, Smad2-dependent and -independent signaling, but not COX. These signaling molecules can be biomarkers of BQ carcinogenesis. PBL, HC and melatonin and other targeting therapy can be used for oral cancer treatment. Methods: ANE-induced MMP-9 expression/secretion of oral epithelial cells and related TGF-?1, Smad-dependent and -independent signaling were studied by MTT assay, RT-PCR, western blotting, immunofluorescent staining, and ELISA. ? Chang et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077297277&doi=10.18632%2faging.102565&partnerID=40&md5=82e7a187bef5edbf15489ad6fc5b2573 https://scholars.lib.ntu.edu.tw/handle/123456789/570626 |
ISSN: | 1945-4589 | DOI: | 10.18632/aging.102565 | SDG/Keyword: | 2-hydroxychavicol; arecoline; eugenol; gelatinase B; melatonin; MMP9 protein, human; plant extract; Smad2 protein; SMAD2 protein, human; transforming growth factor beta; Areca; cell survival; chemistry; drug effect; epithelium cell; gene expression regulation; genetics; human; metabolism; plant leaf; tumor cell line; Areca; Arecoline; Cell Line, Tumor; Cell Survival; Epithelial Cells; Eugenol; Gene Expression Regulation; Humans; Matrix Metalloproteinase 9; Melatonin; Plant Extracts; Plant Leaves; Smad2 Protein; Transforming Growth Factor beta |
Appears in Collections: | 臨床牙醫學研究所 |
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