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Arecoline-stimulated placenta growth factor production in gingival epithelial cells: modulation by curcumin
1Graduate 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.
Objective:
Placenta growth factor (PlGF) is associated with the progression and prognosis of oral cancer.
Materials And 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.
Conclusion:
Arecoline-induced PlGF synthesis is probably mediated by reactive oxygen species/ERK pathways, and curcumin may be an useful agent in controlling oral carcinogenesis.
