The induction of prostaglandin E2 production, interleukin-6 production, cell cycle arrest, and cytotoxicity in primary oral keratinocytes and KB cancer cells by areca nut ingredients is differentially regulated by MEK/ERK activation

The Journal of Biological Chemistry
Mei-Chi ChangJiiang-Huei Jeng

Abstract

There are about 200-600 million betel quid (BQ) chewers in the world. BQ chewing is one of the major risk factor of hepatocarcinoma, oropharyngeal, and esophagus cancers in Taiwan, India, and Southeast Asian countries. Thus, the precise molecular mechanisms deserve investigation. We used cultured primary keratinocytes and KB cells, RT-PCR, flow cytometry, Western blotting, and ELISA to evaluate whether alterations in early gene expression is crucial in the carcinogenic processes of BQ. We observed the induction of c-Fos mRNA expression in human gingival keratinocyte (GK) and KB carcinoma cells by areca nut (AN) extract and arecoline. A maximal increment in c-fos gene expression was shown at about 30 min after challenge. AN extract (100-800 microg/ml) and arecoline (0.1-0.8 mM) also stimulated ERK1/ERK2 phosphorylation with a maximal stimulation at 5-10 min of exposure. Pretreatment by U0126 (30 microM), a MEK inhibitor, markedly inhibited the c-Fos, cyclooxygenase-2 (COX-2), and IL-6 mRNA expression of the KB epithelial cells. In addition, U0126 and PD98059 (50 microM) also decreased AN extract- and arecoline-associated PGE2 and IL-6 production in GK and KB cells. However, U0126 by itself arrested the cells in G0/G1 phase, but ...Continue Reading

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Citations

Aug 19, 2011·Clinical Oral Investigations·Shuei-Kuen TsengJiiang-Huei Jeng
Mar 5, 2015·Journal of the Formosan Medical Association = Taiwan Yi Zhi·Chien-Yang YehJiiang-Huei Jeng
Dec 4, 2010·Journal of the Formosan Medical Association = Taiwan Yi Zhi·Yu-Chi LiuYoung-Chau Liu
Apr 25, 2012·Journal of the Formosan Medical Association = Taiwan Yi Zhi·Shiuan-Shinn LeeYu-Chao Chang
May 5, 2009·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Chia-Chi WangTong-Rong Jan
Sep 10, 2014·Journal of Biomedical Science·Tzer-Min KuoYing-Chin Ko
Apr 15, 2009·Journal of Periodontal Research·G S Thangjam, P Kondaiah
Jan 29, 2008·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Shun-Fa YangYu-Chao Chang
Aug 5, 2008·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Stephen Cox, Hans Zoellner
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Jan 5, 2011·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Shiuan-Shinn LeeYu-Chao Chang
Apr 26, 2014·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Mafaz UllahHans Zoellner
Feb 4, 2014·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Jian-Ping DaiKang-Sheng Li

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