title: Arecoline inhibits epithelial cell viability by upregulating the apoptosis pathway: implication for oral submucous fibrosis.
abstract: Oral submucous fibrosis (OSF) is a chronic inflammatory disease characterized by the accumulation of excess collagen, and areca nut chewing has been proposed as a significant etiological factor for disease manifestation. However, the underlying molecular mechanisms regarding areca nut chewing-induced OSF are only partially understood. Herein, we reported that arecoline markedly induced morphologic change in HaCaT epithelial cells, but had no obvious effect on Hel fibroblast cells. MTS assay revealed that arecoline significantly suppressed HaCaT cell viability. Moreover, flow cytometric analysis indicated that arecoline substantially promoted HaCaT cell, but not Hel cell apoptosis in a dose-dependent manner. Furthermore, arecoline-induced HaCaT cell apoptosis was found to be associated with increased expression and activation of cleaved-Bid, cleaved-PARA and cleaved-caspase-3. Collectively, our results suggest that HaCaT epithelial cells are more sensitive than Hel fibroblast cells to arecoline-induced cytotoxicity, which may be involved in the pathogenesis of OSF.
authors.affiliation: Dental Medical Center, Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Powder Metallurgy Research Institute of Central South University, Changsha, Hunan, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Changsha Stomatological Hospital, Changsha, Hunan, P.R. China.
authors.forename: Zhong-Su
authors.initials: ZS
authors.lastname: Zhou
authors.affiliation: Changsha Stomatological Hospital, Changsha, Hunan, P.R. China.
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Zhang
authors.affiliation: Changsha Stomatological Hospital, Changsha, Hunan, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Dental Medical Center, Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China.
authors.forename: Ying-Fang
authors.initials: YF
authors.lastname: Wu
authors.affiliation: Changsha Stomatological Hospital, Changsha, Hunan, P.R. China.
authors.forename: Ming-Hai
authors.initials: MH
authors.lastname: Bai
authors.affiliation: Dental Medical Center, Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China.
authors.forename: Ji-Jia
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Taiwan Taipei Dental Sciences, Taipei, Taiwan, R.O.C.
authors.forename: Shi-Rong
authors.initials: SR
authors.lastname: Lin
authors.affiliation: Dental Medical Center, Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China.
authors.forename: Jie-Ying
authors.initials: JY
authors.lastname: Peng
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001114:Areca / Q000009:adverse effects; D001115:Arecoline / Q000494:pharmacology*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D018679:Cholinergic Agonists / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D005247:Feeding Behavior; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D009061:Mouth Mucosa / Q000473:pathology; D009914:Oral Submucous Fibrosis / Q000139:chemically induced / Q000473:pathology*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D018679:Cholinergic Agonists; D001115:Arecoline; D053148:Caspase 3