Arecoline-stimulated placenta growth factor production in gingival epithelial cells: modulation by curcumin

作者：Cheng S J; Ko H H; Cheng S L; Lee J J; Chen H M; Chang H H; Kok S H; Kuo M Y P; Chiang C P^*

来源：Oral Diseases, 2013, 19(5): 513-518.

DOI：10.1111/odi.12034

• arecoline
• placenta growth factor
• oral cancer
• keratinocyte
• curcumin

OBJECTIVE: Placenta growth factor (PlGF) is associated with the progression and prognosis of oral cancer. %26lt;br%26gt;MATERIALS AND METHODS: This study used ELISA, quantitative polymerase chain reaction, and Western blotting to study the arecoline-stimulated (PlGF) protein or mRNA expression inhuman gingival epithelial S-G cells. %26lt;br%26gt;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-kappa B 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 mu M curcumin and 4 mM NAC significantly inhibited arecoline-induced ERK activation. Furthermore, 10 mu M curcumin completely blocked arecoline-induced PlGF mRNA expression. %26lt;br%26gt;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.

• 出版日期2013-7