https://scholars.lib.ntu.edu.tw/handle/123456789/569434
Title: | Areca nut components affect COX-2, cyclin B1/cdc25C and keratin expression, PGE2 production in keratinocyte is related to reactive oxygen species, CYP1A1, Src, EGFR and Ras signaling | Authors: | Chang M.-C. YI-JANE CHEN HSIAO-HUA CHANG Chan C.-P. Yeh C.-Y. YIN-LIN WANG Cheng R.-H. Hahn L.-J. JIIANG-HUEI JENG |
Issue Date: | 2014 | Publisher: | Public Library of Science | Journal Volume: | 9 | Journal Issue: | 7 | Start page/Pages: | e101959 | Source: | PLoS ONE | Abstract: | Aims: Chewing of betel quid (BQ) increases the risk of oral cancer and oral submucous fibrosis (OSF), possibly by BQ-induced toxicity and induction of inflammatory response in oral mucosa. Methods: Primary gingival keratinocytes (GK cells) were exposed to areca nut (AN) components with/without inhibitors. Cytotoxicity was measured by 3-(4,5-dimethyl- thiazol-2-yl)-2,5-diphenyl- tetrazolium bromide (MTT) assay. mRNA and protein expression was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. PGE2/PGF2α production was measured by enzyme-linked immunosorbent assays. Results: Areca nut extract (ANE) stimulated PGE 2/PGF2α production, and upregulated the expression of cyclooxygenase-2 (COX-2), cytochrome P450 1A1 (CYP1A1) and hemeoxygenase-1 (HO-1), but inhibited expression of keratin 5/14, cyclinB1 and cdc25C in GK cells. ANE also activated epidermal growth factor receptor (EGFR), Src and Ras signaling pathways. ANE-induced COX-2, keratin 5, keratin 14 and cdc25C expression as well as PGE2 production were differentially regulated by α-naphthoflavone (a CYP 1A1/1A2 inhibitor), PD153035 (EGFR inhibitor), pp2 (Src inhibitor), and manumycin A (a Ras inhibitor). ANE-induced PGE 2 production was suppressed by piper betle leaf (PBL) extract and hydroxychavicol (two major BQ components), dicoumarol (a NAD(P)H:Quinone Oxidoreductase - NQO1 inhibitor) and curcumin. ANE-induced cytotoxicity was inhibited by catalase and enhanced by dicoumarol, suggesting that AN components may contribute to the pathogenesis of OSF and oral cancer via induction of aberrant differentiation, cytotoxicity, COX-2 expression, and PGE 2/PGF2αproduction. Conclusions: CYP4501A1, reactive oxygen species (ROS), EGFR, Src and Ras signaling pathways could all play a role in ANE-induced pathogenesis of oral cancer. Addition of PBL into BQ and curcumin consumption could inhibit the ANE-induced inflammatory response. ? 2014 Chang et al. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84904647226&doi=10.1371%2fjournal.pone.0101959&partnerID=40&md5=54a6da533c658fc8537a0235dff5d2d4 https://scholars.lib.ntu.edu.tw/handle/123456789/569434 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0101959 | SDG/Keyword: | 4 (3 bromoanilino) 6,7 dimethoxyquinazoline; 4 amino 7 tert butyl 5 (4 chlorophenyl)pyrazolo[3,4 d]pyrimidine; alpha naphthoflavone; betel extract; catalase; curcumin; cyclin B1; cyclooxygenase 2; cytochrome P450 1A1; cytokeratin 14; cytokeratin 5; dicoumarol; epidermal growth factor receptor; heme oxygenase 1; keratin; manumycin; prostaglandin E2; prostaglandin F2 alpha; Ras protein; reactive oxygen metabolite; CCNB1 protein, human; CDC25C protein, human; curcumin; cyclin B1; cyclooxygenase 2; CYP1A1 protein, human; cytochrome P450 1A1; dicoumarol; EGFR protein, human; epidermal growth factor receptor; heme oxygenase 1; HMOX1 protein, human; keratin; plant extract; prostaglandin E2; protein tyrosine kinase; protein tyrosine phosphatase; PTGS2 protein, human; Ras protein; reactive oxygen metabolite; article; betel nut; cancer risk; controlled study; cytotoxicity; enzyme inhibition; enzyme linked immunosorbent assay; enzyme synthesis; human; human cell; inflammation; keratinocyte; mouth cancer; mouth disease; mouth mucosa; MTT assay; pathogenesis; protein analysis; protein expression; protein function; reverse transcription polymerase chain reaction; signal transduction; upregulation; Western blotting; Areca; biosynthesis; cell culture; chemistry; drug effects; gene expression; genetics; gingiva; keratinocyte; metabolism; pathology; Areca; cdc25 Phosphatases; Cells, Cultured; Curcumin; Cyclin B1; Cyclooxygenase 2; Cytochrome P-450 CYP1A1; Dicumarol; Dinoprostone; Gene Expression; Gingiva; Heme Oxygenase-1; Humans; Keratinocytes; Keratins; Plant Extracts; ras Proteins; Reactive Oxygen Species; Receptor, Epidermal Growth Factor; Signal Transduction; src-Family Kinases |
Appears in Collections: | 臨床牙醫學研究所 |
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