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

Authors

  • S-J Cheng,

    1. Graduate Institute of Clinical Dentistry, National Taiwan University, Taipei, Taiwan
    2. School of Dentistry, National Taiwan University, Taipei, Taiwan
    3. Department of Dentistry, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • H-H Ko,

    1. Graduate Institute of Clinical Dentistry, National Taiwan University, Taipei, Taiwan
    2. Department of Dentistry, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • S-L Cheng,

    1. Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan
    2. Department of Chemical Engineering and Materials Science, Yuan-Ze University, Chung-Li, Taiwan
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  • J-J Lee,

    1. School of Dentistry, National Taiwan University, Taipei, Taiwan
    2. Department of Dentistry, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • H-M Chen,

    1. Graduate Institute of Clinical Dentistry, National Taiwan University, Taipei, Taiwan
    2. School of Dentistry, National Taiwan University, Taipei, Taiwan
    3. Department of Dentistry, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    4. Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
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  • H-H Chang,

    1. School of Dentistry, National Taiwan University, Taipei, Taiwan
    2. Department of Dentistry, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • S-H Kok,

    1. School of Dentistry, National Taiwan University, Taipei, Taiwan
    2. Department of Dentistry, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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  • MY-P Kuo,

    Corresponding author
    1. School of Dentistry, National Taiwan University, Taipei, Taiwan
    2. Department of Dentistry, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    3. Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
    • Graduate Institute of Clinical Dentistry, National Taiwan University, Taipei, Taiwan
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  • C-P Chiang

    Corresponding author
    1. School of Dentistry, National Taiwan University, Taipei, Taiwan
    2. Department of Dentistry, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
    3. Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
    • Graduate Institute of Clinical Dentistry, National Taiwan University, Taipei, Taiwan
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Correspondence: Chun-Pin Chiang and Mark Yen-Ping Kuo, Department of Dentistry, National Taiwan University Hospital, No.1, Chang-Te Street, Taipei 10048, Taiwan. Tel: +886 2 2312 3456 Ext. 66855, Fax: +886 2 23893853, E-mails: cpchiang@ntu.edu.tw; oddie@ntu.edu.tw

Abstract

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.

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