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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalToxicology
Volume220
Issue number2-3
DOIs
Publication statusPublished - Mar 15 2006

Fingerprint

Arecoline
KB Cells
Cell growth
Cell Cycle
Epithelial Cells
Cells
Apoptosis
Growth
lissamine rhodamine B
Carcinogenesis
Oral Submucous Fibrosis
Areca
CDC2 Protein Kinase
M Phase Cell Cycle Checkpoints
Leukoplakia
Cyclin B1
Cell Cycle Proteins
Proteins
Cyclins
Deregulation

Keywords

  • Apoptosis
  • Areca nut
  • Arecoline
  • Betel quid
  • Carcinogenesis
  • Cell cycle
  • Epithelial cells

ASJC Scopus subject areas

  • Toxicology

Cite this

Lee, P. H., Chang, M. C., Chang, W. H., Wang, T. M., Wang, Y. J., Hahn, L. J., ... Jeng, J. H. (2006). Prolonged exposure to arecoline arrested human KB epithelial cell growth: Regulatory mechanisms of cell cycle and apoptosis. Toxicology, 220(2-3), 81-89. https://doi.org/10.1016/j.tox.2005.07.026

Prolonged exposure to arecoline arrested human KB epithelial cell growth : Regulatory mechanisms of cell cycle and apoptosis. / Lee, Po Hsuen; Chang, Mei Chi; Chang, Wen Hui; Wang, Tong Mei; Wang, Ying Jen; Hahn, Liang Jiunn; Ho, Yuan Soon; Lin, Chuan Yu; Jeng, Jiiang Huei.

In: Toxicology, Vol. 220, No. 2-3, 15.03.2006, p. 81-89.

Research output: Contribution to journalArticle

Lee, PH, Chang, MC, Chang, WH, Wang, TM, Wang, YJ, Hahn, LJ, Ho, YS, Lin, CY & Jeng, JH 2006, 'Prolonged exposure to arecoline arrested human KB epithelial cell growth: Regulatory mechanisms of cell cycle and apoptosis', Toxicology, vol. 220, no. 2-3, pp. 81-89. https://doi.org/10.1016/j.tox.2005.07.026
Lee, Po Hsuen ; Chang, Mei Chi ; Chang, Wen Hui ; Wang, Tong Mei ; Wang, Ying Jen ; Hahn, Liang Jiunn ; Ho, Yuan Soon ; Lin, Chuan Yu ; Jeng, Jiiang Huei. / Prolonged exposure to arecoline arrested human KB epithelial cell growth : Regulatory mechanisms of cell cycle and apoptosis. In: Toxicology. 2006 ; Vol. 220, No. 2-3. pp. 81-89.
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