title: Areca nut extract represses migration and differentiation while activating matrix metalloproteinase-9 of normal gingival epithelial cells.
abstract: OBJECTIVE
  Areca (betel) chewing is associated with an increase in the incidence of periodontal diseases. Aberrations in matrix metalloproteinase (MMP) expression have been reported to be associated with periodontal disease. This study investigated the effects of areca nut extract on MMP activity and the phenotype of human gingival epithelial cells.
  
  
  METHODS
  Reverse transcription-polymerase chain reaction, western blotting and gelatin zymography were used to assay MMPs. Cell viability, mobility and detachment assays were performed to characterize the phenotypic impact. Confocal microscopy was employed to evaluate cell aggregation and the distribution of E-cadherin and F-actin.
  
  
  RESULTS
  Treatment of gingival epithelial cells with 10 microg/mL of areca nut extract reduced its cell viability. Treatment with 5 and 10 microg/mL of areca nut extract for 24 h activated MMP-9 but not MMP-2 in gingival epithelial cells. This activation could be nuclear factor-kappaB dependent and was abrogated by 10 microM curcumin. Areca nut extract also reduced the migration and detachment of gingival epithelial cells. The differentiated cell-cell contact of gingival epithelial cells was markedly impaired by areca nut extract. This was accompanied by a disruption of distribution of E-cadherin and F-actin.
  
  
  CONCLUSIONS
  The areca nut extract-mediated activation of MMP-9 in gingival epithelial cells could signify a potential periodontal pathogenesis in areca chewers. The areca nut extract-mediated inhibition of cell viability and migration, together with the changed aggregation in gingival epithelial cells, suggests that impairment of the re-epithelization underlies the process and this, in turn, might exacerbate gingival inflammation.
authors.affiliation: Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Tseng
authors.forename: K-W
authors.initials: KW
authors.lastname: Chang
authors.forename: C-J
authors.initials: CJ
authors.lastname: Liu
authors.forename: C-Y
authors.initials: CY
authors.lastname: Lin
authors.forename: S-C
authors.initials: SC
authors.lastname: Yang
authors.forename: S-C
authors.initials: SC
authors.lastname: Lin
mesh_terms: D001114:Areca / Q000009:adverse effects*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010936:Plant Extracts / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D020780:Matrix Metalloproteinase 9; D003474:Curcumin