Carcinogenesis Advance Access originally published online on May 22, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis, Vol. 24, No. 8, 1301-1315,
August 2003
© 2003 Oxford University Press
CANCER BIOLOGY |
Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-
production of oral epithelial cells by areca nut extract and arecoline
Laboratory of Dental Pharmacology and Toxicology, Department of Dentistry, National Taiwan University Hospital and National Taiwan University College of Medicine, Taiwan
1 Graduate Institute of Environmental Medicine, National Cheng-Kung University, Taiwan
2 Department of Pediatrics, National Taiwan University Hospital and Graduate Institute of Clinical Medicine, National Taiwan University, Taiwan
3 Department of Dentistry, Chang-Gung Memorial Hospital, Taipei, Taiwan
4 Department of Biomedical Technology, Taipei Medical College, Taipei, Taiwan
5 Team of Biomedical Science, Chang-Gung Institute of Technology, 261 Wen-Hwa 1 Road, Kwei-Shan, Taoyuan 33333, Taiwan
6 To whom correspondence should be addressed. Tel: +886 3 2118999; Fax: +886 3 2118866; Email: mcchang{at}mail.cgit.edu.tw
Betel quid (BQ) chewing is an etiologic factor of oral cancer and submucus fibrosis (OSF). Keratinocyte inflammation is crucial for the pathogenesis of cancer and tissue fibrosis. We found that areca nut (AN) extract (100–400 µg/ml) induced PGE2 production by KB cells by 2.34- to 23.1-fold and also TNF-
production by gingival keratinocytes (GK). Arecoline (0.2–1.2 mM) elevated PGE2 production by KB cells by 2.5- to 6.1-fold. AN extract (200–400 µg/ml) also induced IL-6 production by GK (7.5- to 8.4-fold) and KB cells. In contrast, arecoline (0.1–1.2 mM) suppressed IL-6 production by GK and KB cells, with 42–81 and 41–63% inhibition, respectively. A 48 h exposure of GK to 800–1200 µg/ml AN extract led to 37–69% cell death. Arecoline cytotoxicity to GK was noted at concentrations of 0.8–1.2 mM, which led to 28–38% cell death. AN extract (400–800 µg/ml) induced Cox-2 and IL-6 mRNA expression and also COX-2 protein production by KB cells. IL-6 (5–100 ng/ml) suppressed GK growth by 20–33%, but enhanced oral fibroblast (OMF) and KB cell growth. PGE2 (0.05–5 µg/ml) and anti-IL-6 antibody (ab) (50–1000 ng/ml) showed little effect on GK and KB cell growth. Incubation of GK and KB cells with aspirin, anti-IL-6 ab and anti-TNF- ab showed little effect on arecoline- and AN-induced cytotoxicity, cell cycle arrest and apoptosis. Exposure to anti-TNF- ab slightly affected arecoline- and AN-modulated PGE2 and IL-6 production by GK and KB cells. Arecoline- and AN-conditioned medium decreased phytohemagglutinin-mediated CD4+ and CD8+ T cell activation. These results indicate that BQ chewing contributes to the pathogenesis of cancer and OSF by impairing T cell activation and by induction of PGE2, TNF- and IL-6 production, which affect oral mucosal inflammation and growth of OMF and oral epithelial cells.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S.-L. Chiang, P.-H. Chen, C.-H. Lee, A. M.-S. Ko, K.-W. Lee, Y.-C. Lin, P.-S. Ho, H.-P. Tu, D.-C. Wu, T.-Y. Shieh, et al. Up-regulation of Inflammatory Signalings by Areca Nut Extract and Role of Cyclooxygenase-2 -1195G>A Polymorphism Reveal Risk of Oral Cancer Cancer Res., October 15, 2008; 68(20): 8489 - 8498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-W. Wang, G.-S. Hwang, T.-J. Chen, and P. S. Wang Effects of arecoline on testosterone release in rats Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E497 - E504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-Y. Lin, T.-Y. Chiu, L.-T. Lee, C.-C. Lin, C.-Y. Huang, and K.-C. Huang Betel nut chewing is associated with increased risk of cardiovascular disease and all-cause mortality in Taiwanese men Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1204 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-L. Chiang, S.-S. Jiang, Y.-J. Wang, H.-C. Chiang, P.-H. Chen, H.-P. Tu, K.-Y. Ho, Y.-S. Tsai, I-S. Chang, and Y.-C. Ko Characterization of Arecoline-Induced Effects on Cytotoxicity in Normal Human Gingival Fibroblasts by Global Gene Expression Profiling Toxicol. Sci., November 1, 2007; 100(1): 66 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Sun, S. Sood, N. Li, D. Ramji, P. Yang, R. A. Newman, C. S. Yang, and X. Chen Involvement of the 5-lipoxygenase/leukotriene A4 hydrolase pathway in 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamster cheek pouch, and inhibition of carcinogenesis by its inhibitors Carcinogenesis, September 1, 2006; 27(9): 1902 - 1908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Guh, L.-Y. Chuang, and H.-C. Chen Betel-quid use is associated with the risk of the metabolic syndrome in adults Am. J. Clinical Nutrition, June 1, 2006; 83(6): 1313 - 1320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Y. Lu, K.-W. Chang, C.-J. Liu, Y.-H. Tseng, H.-H. Lu, S.-Y. Lee, and S.-C. Lin Ripe areca nut extract induces G1 phase arrests and senescence-associated phenotypes in normal human oral keratinocyte Carcinogenesis, June 1, 2006; 27(6): 1273 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Tseng Betel Nut Chewing Is Independently Associated With Urinary Albumin Excretion Rate in Type 2 Diabetic Patients Diabetes Care, February 1, 2006; 29(2): 462 - 463. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Li, S. Sood, S. Wang, M. Fang, P. Wang, Z. Sun, C. S. Yang, and X. Chen Overexpression of 5-Lipoxygenase and Cyclooxygenase 2 in Hamster and Human Oral Cancer and Chemopreventive Effects of Zileuton and Celecoxib Clin. Cancer Res., March 1, 2005; 11(5): 2089 - 2096. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-C. Chang, H.-L. Wu, J.-J. Lee, P.-H. Lee, H.-H. Chang, L.-J. Hahn, B.-R. Lin, Y.-J. Chen, and J.-H. Jeng 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 J. Biol. Chem., December 3, 2004; 279(49): 50676 - 50683. [Abstract] [Full Text] [PDF]
|
|