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

Abstract:

: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 85kDa 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 24h 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.

journal_name

Oral Oncol

journal_title

Oral oncology

authors

Liu SY,Liu YC,Huang WT,Huang GC,Chen TC,Lin MH

doi

10.1016/j.oraloncology.2006.11.018

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

1026-33

issue

10

eissn

1368-8375

issn

1879-0593

pii

S1368-8375(06)00312-5

journal_volume

43

pub_type

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