title: Arecoline-stimulated placenta growth factor production in gingival epithelial cells: modulation by curcumin.
abstract: OBJECTIVE
  Placenta growth factor (PlGF) is associated with the progression and prognosis of oral cancer.
  
  
  METHODS
  This study used ELISA, quantitative polymerase chain reaction, and Western blotting to study the arecoline-stimulated (PlGF) protein or mRNA expression in human gingival epithelial S-G cells.
  
  
  RESULTS
  Arecoline, a major areca nut alkaloid and an oral carcinogen, could stimulate PlGF protein synthesis in S-G cells in a dose- and time-dependent manner. The levels of PlGF protein secretion increased about 3.1- and 3.8-fold after 24-h exposure to 0.4 and 0.8 mM arecoline, respectively. Pretreatment with antioxidant N-acetyl-l-cysteine (NAC) and ERK inhibitor PD98059, but not NF-κB inhibitor Bay 11-7082, JNK inhibitor SP600125, p38 MAPK inhibitor SB203580, and PI3-K inhibitor LY294002, significantly reduced arecoline-induced PlGF protein synthesis. ELISA analyses demonstrated that NAC and PD98059 reduced about 43% and 38% of the arecoline-induced PlGF protein secretion, respectively. However, combined treatment with NAC and PD98059 did not show additive effect. Moreover, 10 μM curcumin and 4 mM NAC significantly inhibited arecoline-induced ERK activation. Furthermore, 10 μM curcumin completely blocked arecoline-induced PlGF mRNA expression.
  
  
  CONCLUSIONS
  Arecoline-induced PlGF synthesis is probably mediated by reactive oxygen species/ERK pathways, and curcumin may be an useful agent in controlling oral carcinogenesis.
authors.affiliation: Graduate Institute of Clinical Dentistry, National Taiwan University, Taipei, Taiwan; School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Cheng
authors.forename: H-H
authors.initials: HH
authors.lastname: Ko
authors.forename: S-L
authors.initials: SL
authors.lastname: Cheng
authors.forename: J-J
authors.initials: JJ
authors.lastname: Lee
authors.forename: H-M
authors.initials: HM
authors.lastname: Chen
authors.forename: H-H
authors.initials: HH
authors.lastname: Chang
authors.forename: S-H
authors.initials: SH
authors.lastname: Kok
authors.forename: M Y-P
authors.initials: MY
authors.lastname: Kuo
authors.forename: C-P
authors.initials: CP
authors.lastname: Chiang
mesh_terms: D001115:Arecoline / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis*
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D001115:Arecoline; D003474:Curcumin