Prolonged exposure to arecoline arrested human KB epithelial cell growth: Regulatory mechanisms of cell cycle and apoptosis

Po Hsuen Lee, Mei Chi Chang, Wen Hui Chang, Tong Mei Wang, Ying Jen Wang, Liang Jiunn Hahn, Yuan Soon Ho, Chuan Yu Lin, Jiiang Huei Jeng

研究成果: Article同行評審

52 引文 斯高帕斯(Scopus)

摘要

Arecoline, the main areca alkaloid in betel quid (BQ), is reported to have cytotoxic, genotoxic, and mutagenic effects in various cells. It shows strong correlation to the incidence of oral submucous fibrosis, leukoplakia, and oral cancer. To clarify the role of arecoline in BQ-induced carcinogenesis, primary human gingival keratinocyes (GK) and human KB epithelial cells were used for studying the molecular mechanisms of arecoline-mediated cell cycle deregulation for comparison. After 24 h of exposure, arecoline (0.2-0.8 mM) inhibited KB cell growth in a dose- and time-dependent manner with a reduction in cell number by 27-37 and 37-58%, respectively, as determined by 3-(4,5-dimethyl-thiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. Incubation of KB cells with arecoline (0.1-0.4 mM) caused late-S and G2/M phases' cell cycle arrest. Western blot analysis revealed that arecoline induced cyclin Bl, Wee 1, and phosphorylated cdc2 protein levels whereas it declined p21 protein expression in KB cancer cells. Nevertheless, arecoline induced p21, but decreased cdc2 and cyclin B1 protein levels in GK. We demonstrated that higher concentrations of arecoline (0.2-1.2 mM) induced both cell necrosis and apoptosis as detected by DNA fragmentation and Annexin V-PI staining after long-term (48 h) treatment. Our results suggest that differential regulation of S and/or G2/M cell cycle-related proteins in the GK and KB cells play a crucial role in different stages of BQ-mediated carcinogenesis.

原文English
頁(從 - 到)81-89
頁數9
期刊Toxicology
220
發行號2-3
DOIs
出版狀態Published - 2006 三月 15

All Science Journal Classification (ASJC) codes

  • 毒理學

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