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.

<h4>Aims</h4>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.<h4>Methods</h4>Primary gingival keratinocytes (GK cells) were exposed to areca n...

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Autores principales:	Mei-Chi Chang, Yi-Jane Chen, Hsiao-Hua Chang, Chiu-Po Chan, Chien-Yang Yeh, Yin-Lin Wang, Ru-Hsiu Cheng, Liang-Jiunn Hahn, Jiiang-Huei Jeng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce20d7ef520a48c28c9a2a36e30d8174
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spelling	oai:doaj.org-article:ce20d7ef520a48c28c9a2a36e30d81742021-11-25T06:07:34ZAreca 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.1932-620310.1371/journal.pone.0101959https://doaj.org/article/ce20d7ef520a48c28c9a2a36e30d81742014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25051199/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Areca nut extract (ANE) stimulated PGE2/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 PGE2 production was suppressed by piper betle leaf (PBL) extract and hydroxychavicol (two major BQ components), dicoumarol (a<h4>Nad(p)h</h4>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 PGE2/PGF2α production.<h4>Conclusions</h4>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.Mei-Chi ChangYi-Jane ChenHsiao-Hua ChangChiu-Po ChanChien-Yang YehYin-Lin WangRu-Hsiu ChengLiang-Jiunn HahnJiiang-Huei JengPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e101959 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mei-Chi Chang Yi-Jane Chen Hsiao-Hua Chang Chiu-Po Chan Chien-Yang Yeh Yin-Lin Wang Ru-Hsiu Cheng Liang-Jiunn Hahn Jiiang-Huei Jeng 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.
description	<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Areca nut extract (ANE) stimulated PGE2/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 PGE2 production was suppressed by piper betle leaf (PBL) extract and hydroxychavicol (two major BQ components), dicoumarol (a<h4>Nad(p)h</h4>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 PGE2/PGF2α production.<h4>Conclusions</h4>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.
format	article
author	Mei-Chi Chang Yi-Jane Chen Hsiao-Hua Chang Chiu-Po Chan Chien-Yang Yeh Yin-Lin Wang Ru-Hsiu Cheng Liang-Jiunn Hahn Jiiang-Huei Jeng
author_facet	Mei-Chi Chang Yi-Jane Chen Hsiao-Hua Chang Chiu-Po Chan Chien-Yang Yeh Yin-Lin Wang Ru-Hsiu Cheng Liang-Jiunn Hahn Jiiang-Huei Jeng
author_sort	Mei-Chi Chang
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.
title_short	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.
title_full	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.
title_fullStr	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.
title_full_unstemmed	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.
title_sort	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.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ce20d7ef520a48c28c9a2a36e30d8174
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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.

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