Areca nut-induced buccal mucosa fibroblast contraction and its signaling: a potential role in oral submucous fibrosis--a precancer condition
Open Access
- 24 January 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis
- Vol. 34 (5) , 1096-1104
Abstract
Betel quid (BQ) chewing is an oral habit that increases the risk of oral cancer and oral submucous fibrosis (OSF), a precancerous condition showing epithelial atrophy and tissue fibrosis. Persistent fibroblast contraction may induce the fibrotic contracture of tissue. In this study, we found that areca nut extract (ANE) (200–1200 µg/ml) stimulated buccal mucosa fibroblast (OMF)-populated collagen gel contraction. Arecoline but not arecaidine—two areca alkaloids, slightly induced the OMF contraction. Exogenous addition of carboxylesterase (2U/ml) prevented the arecoline- but not ANE-induced OMF contraction. OMF expressed inositol triphosphate (IP3) receptors. ANE-induced OMF (800 µg/ml) contraction was inhibited by U73122 [phospholipase C (PLC) inhibitor] and 2-aminoethoxydiphenyl borate (IP3 receptor antagonist), respectively. Ethylene glycol tetraacetic acid and verapamil, two calcium mobilization modulators, also suppressed the ANE-induced OMF contraction. ANE induced calcium/calmodulin kinase II and myosin light chain (MLC) phosphorylation in OMF. Moreover, W7 (a Ca 2+ /calmodulin inhibitor), HA1077 (Rho kinase inhibitor), ML-7 (MLC kinase inhibitor) and cytochalasin B (actin filament polymerization inhibitor) inhibited the ANE-induced OMF contraction. Although ANE elevated reactive oxygen species (ROS) level in OMF, catalase, superoxide dismutase and N -acetyl- l -cysteine showed no obvious effect on ANE-elicited OMF contraction. These results indicate that BQ chewing may affect the wound healing and fibrotic processes in OSF via inducing OMF contraction by ANE and areca alkaloids. AN components-induced OMF contraction was related to PLC/IP3/Ca 2+ /calmodulin and Rho signaling pathway as well as actin filament polymerization, but not solely due to ROS production.Keywords
This publication has 52 references indexed in Scilit:
- A review of betel quid chewing, oral cancer and precancer in Mainland ChinaOral Oncology, 2007
- Oral submucous fibrosis: Review on aetiology and pathogenesisOral Oncology, 2006
- Ca2+ Influx through L-type Ca2+ Channels Controls the Trailing Tail Contraction in Growth Factor-induced Fibroblast Cell MigrationJournal of Biological Chemistry, 2005
- Augmented mRNA expression of tissue inhibitor of metalloproteinase-1 in buccal mucosal fibroblasts by arecoline and safrole as a possible pathogenesis for oral submucous fibrosisOral Oncology, 2003
- Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectivesOral Oncology, 2001
- Co-expression of colligin and collagen in oral submucous fibrosis: plausible role in pathogenesisOral Oncology, 2001
- Raised tissue copper levels in oral submucous fibrosisJournal of Oral Pathology & Medicine, 2000
- Deficiency in collagen and fibronectin phagocytosis by human buccal mucosa fibroblasts in vitro as a possible mechanism for oral submucous fibrosisJournal of Oral Pathology & Medicine, 1999
- Oral submucous fibrosis. A reviewAustralian Dental Journal, 1996
- Etiology of oral submucous fibrosis with special reference to the role of areca nut chewingJournal of Oral Pathology & Medicine, 1995