Areca nut-induced buccal mucosa fibroblast contraction and its signaling: A potential role in oral submucous fibrosis-a precancer condition

Mei Chi Chang, Li Deh Lin, Hui Lin Wu, Yuan Soon Ho, Hsiang Chi Hsien, Tong Mei Wang, Po Yuan Jeng, Ru Hsiu Cheng, Liang Jiunn Hahn, Jiiang Huei Jeng

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25 Citations (Scopus)

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 (2 U/ml) prevented the arecoline- but not ANEinduced 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 Ca2+/ 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/Ca2+/calmodulin and Rho signaling pathway as well as actin filament polymerization, but not solely due to ROS production.

Original languageEnglish
Pages (from-to)1096-1104
Number of pages9
JournalCarcinogenesis
Volume34
Issue number5
DOIs
Publication statusPublished - May 2013

ASJC Scopus subject areas

  • Cancer Research

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  • Cite this

    Chang, M. C., Lin, L. D., Wu, H. L., Ho, Y. S., Hsien, H. C., Wang, T. M., Jeng, P. Y., Cheng, R. H., Hahn, L. J., & Jeng, J. H. (2013). Areca nut-induced buccal mucosa fibroblast contraction and its signaling: A potential role in oral submucous fibrosis-a precancer condition. Carcinogenesis, 34(5), 1096-1104. https://doi.org/10.1093/carcin/bgt012