Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells

J. H. Jeng, Y. J. Wang, W. H. Chang, H. L. Wu, C. H. Li, B. J. Uang, J. J. Kang, J. J. Lee, L. J. Hahn, B. R. Lin, M. C. Chang

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Abstract

Betel quid (BQ) chewing shows a strong correlation to the incidence of oral submucous fibrosis (OSF), leukoplakia and oral cancer. BQ contains mainly areca nut, lime, Piper betle leaf (PBL) and the inflorescence of P. betle (IPB). Hydroxychavicol (4-allyl-catechol, HC), as a major phenolic compound in PBL and IPB, is shown to induce oxidative stress, glutathione (GSH) depletion and cell cycle deregulation. Using bivariate BrdU/PI flow cytometry, KB cells in DNA synthesis (S phase) are shown to be sensitive to the toxic effect of HC and show cell cycle arrest and apoptosis following exposure to 0.1 and 0.3 mM HC. HC-induced apoptosis and cell cycle arrest are associated with mitochondrial membrane potential (Δψm) depolarization as revealed by a decrease in rhodamine fluorescence. N-acetyl-L-cysteine (1 mM), superoxide dismutase (100 U/ml) and catalase (1000 U/ml) were effective in prevention of HC-induced GSH depletion (as indicated by chloromethylfluorescein fluorescence), reactive oxygen species (ROS) production (by dichlorofluorescein fluorescence), cell cycle arrest and apoptosis. However, dimethylthiourea (2 mM), neocuproine (1 mM), 1,10-phenanthroline (200 μM) and desferrioxamine (0.5 mM) showed little effect on HC-induced cell changes. HC elevated the cellular and mitochondrial GSH levels at moderate concentrations (0.05-0.1 mM), whereas at a concentration of 0.3 mM, inhibitory effects were noted. These results indicate that HC consumption may be associated with BQ-chewing-related oral mucosal diseases via GSH depletion, ROS production, mitochondrial dysfunction, cell cycle disturbance and the induction of apoptosis. These events are related to the production of superoxide radicals and hydrogen peroxide.

Original languageEnglish
Pages (from-to)83-96
Number of pages14
JournalCellular and Molecular Life Sciences
Volume61
Issue number1
DOIs
Publication statusPublished - 2004 Jan 1

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Keywords

  • Apoptosis
  • Betel quid
  • Cell cycle
  • Glutathione
  • Hydroxychavicol
  • Mitochondrial membrane potential
  • Reactive oxygen species

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Jeng, J. H., Wang, Y. J., Chang, W. H., Wu, H. L., Li, C. H., Uang, B. J., Kang, J. J., Lee, J. J., Hahn, L. J., Lin, B. R., & Chang, M. C. (2004). Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells. Cellular and Molecular Life Sciences, 61(1), 83-96. https://doi.org/10.1007/s00018-003-3272-8