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.
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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DOI：
10.1371/journal.pone.0101959
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Jeng JH
中科院分区：
文献类型：
--
作者：
Chang MC;Chen YJ;Chang HH;Chan CP;Yeh CY;Wang YL;Cheng RH;Hahn LJ;Jeng JH
咀嚼槟榔（BQ）增加了口腔癌和口腔粘膜下纤维性变（OSF）的风险，这可能是由于BQ诱导的毒性和诱导口腔粘膜的炎症反应。将原代牙龈角质形成细胞（GK细胞）暴露于含/不含抑制剂的槟榔（AN）成分。通过3-（4，5-二甲基-噻唑-2-基）-2，5-二苯基-溴化四唑（MTT）测定来测量细胞毒性。通过逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法检测mRNA和蛋白质表达。酶联免疫吸附试验测定PGE 2/PGF 2 α的产生。槟榔提取物（ANE）可促进GK细胞PGE 2/PGF 2 α的产生，上调细胞色素P450 1A 1（CYP 1A 1）、环氧合酶2（考克斯-2）和血红素加氧酶1（HO-1）的表达，而抑制角蛋白5/14、细胞周期蛋白B1和cdc 25 C的表达。ANE还激活表皮生长因子受体（EGFR）、Src和Ras信号通路。ANE诱导的考克斯-2、角蛋白5、角蛋白14和cdc 25 C的表达以及PGE 2的产生受到α-萘啶酮（α-naphthalenone，一种α-naphthalenone 1A 1/1A 2抑制剂）、PD 153035（EGFR抑制剂）、pp 2（Src抑制剂）和manumycin A（一种Ras抑制剂）的不同调节。ANE诱导的PGE 2产生被胡椒叶（PBL）提取物和羟基胡椒酚（两种主要的BQ组分）、双香豆素（NAD（P）H：醌氧化还原酶-NQO 1抑制剂）和姜黄素抑制。ANE诱导的细胞毒性可被过氧化氢酶抑制，并被双香豆素增强，提示AN组分可能通过诱导OSF和口腔癌的异常分化、细胞毒性、考克斯-2表达和PGE 2/PGF 2 α产生而参与发病。CYP 4501 A1、活性氧（ROS）、EGFR、Src和Ras信号通路均可能在ANE诱导的口腔癌发病中发挥作用。BQ中加入PBL和姜黄素可抑制ANE诱导的炎症反应。
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. 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. 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 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 PGE2/PGF2αproduction. 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.
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影响因子：
4.8
作者：
Chiang, Wei-Fan;Liu, Shyun-Yeu;Chang, Kuo-Wei
通讯作者：
Chang, Kuo-Wei
影响因子：
4.7
作者：
Chang, MC;Ho, YS;Jeng, JH
通讯作者：
Jeng, JH
影响因子：
6.4
作者：
Lin, SC;Lu, SY;Chang, KW
通讯作者：
Chang, KW
影响因子：
4.3
作者：
Buranrat, Benjaporn;Prawan, Auemduan;Kukongviriyapan, Veerapol
通讯作者：
Kukongviriyapan, Veerapol
影响因子：
7.3
作者：
Chang, M. C.;Uang, B. J.;Jeng, J. H.
通讯作者：
Jeng, J. H.