Up-regulation of matrix metalloproteinase-8 by betel quid extract and arecoline and its role in 2D motility

Shyun Yeu Liu, Young Chau Liu, Wen Tsung Huang, Guan Cheng Huang, Tai Chi Chen, Mei Huei Lin

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Betel quid (BQ) and matrix metalloproteinase-8 (MMP-8) play roles in oral diseases. Here, we analyzed the regulation of MMP-8 by BQ and its effect on cell migration. We found that BQ extract (BQE) increased the secretion of an 85 kDa caseinolytic proteinase, specifically precipitated by an anti-MMP-8 antibody, in the culture medium of OECM-1, an oral squamous cell carcinoma (OSCC) cell line. BQE also stimulated MMP-8 secretion in an esophageal carcinoma cell line, CE81T/VGH, in a dose-dependent manner, and MMP-8 protein was maximally expressed at 24 h after BQE treatment in OECM-1. The BQE-induced MMP-8 expression was dose-dependently inhibited by PD98059. Arecoline, the major alkaloid of areca nut, was tested to dose-dependently up-regulate MMP-8 protein level. Moreover, both arecoline- (4.7-fold) and BQE-selected (5.5-fold) CE81T/VGH cells expressed higher MMP-8 protein level and exhibited enhanced two-dimensional (2D) motility (p = 0.009 in both cells) than parental cells. The enhanced motility of arecoline- (p = 0.006) and BQE-selected (p = 0.002) cells was both specifically blocked by an anti-MMP-8 antibody. We conclude that BQ may accelerate tumor migration by stimulating MMP-8 expression through MEK pathway in at least some carcinomas of the upper aerodigestive tract. Furthermore, arecoline may be one of the positive MMP-8 regulators among BQ ingredients.

Original languageEnglish
Pages (from-to)1026-1033
Number of pages8
JournalOral Oncology
Issue number10
Publication statusPublished - Nov 2007


  • Arecoline
  • Betel quid
  • Matrix metalloproteinase
  • MMP-8
  • Oral squamous cell carcinoma

ASJC Scopus subject areas

  • Oncology


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