Inducing the cell cycle arrest and apoptosis of oral KB carcinoma cells by hydroxychavicol: Roles of glutathione and reactive oxygen species

H. L. Wu, L. J. Hahn, J. J. Lee

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Abstract

1. Hydroxychavicol (HC; 10-50 μM), a betel leaf component, was found to suppress the 2% H2O2-induced lucigenin chemiluminescence for 53-75%. HC (0.02-2μM) was also able to trap superoxide radicals generated by a xanthine/xanthine oxidase system with 38-94% of inhibition. Hydroxyl radicals-induced PUC18 plasmid DNA breaks was prevented by HC (1.6-16 μM). 2. A 24-h exposure of KB cells to HC (0.5, 1 mM) resulted in 54-74% cell death as analysed by a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. HC (10, 50 μM) further suppressed the growth of KB cells (15 and 76%, respectively). Long-term colony formation of KB cells was inhibited by 51% with 10 μM HC. 3. Pretreatment of KB cells with 100 μM HC inhibited the attachment of KB cells to type I collagen and fibronectin by 59 and 29%, respectively. 4. Exposure of KB cells to 0.1 mM HC for 24 h resulted in cell cycle arrest at late S and G2/M phase. Increasing the HC concentration to 0.25 and 0.5 mM led to apoptosis as revealed by detection of sub-G0/G1 peaks with a concomitant decrease in the number of cells residing in late S and G2/M phase. 5. Inducing the apoptosis of KB cells by HC was accompanied by marked depletion in reduced form of GSH (>0.2 mM) and the increasing of reactive oxygen species production (>0.1 mM) as analysed by CMF- and DCF-single cell fluorescence flow cytometry. 6. These results indicate that HC exerts antioxidant property at low concentration. HC also inhibits the growth, adhesion and cell cycle progression of KB cells, whereas its induction of KB cell apoptosis (HC>0.1 mM) was accompanied by cellular redox changes.

Original languageEnglish
Pages (from-to)619-630
Number of pages12
JournalBritish Journal of Pharmacology
Volume135
Issue number3
Publication statusPublished - 2002 Jan 1
Externally publishedYes

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Keywords

  • Apoptosis
  • Betel quid
  • Cell cycle
  • Hydroxychavicol
  • Piper betle
  • Reactive oxygen species
  • Redox status

ASJC Scopus subject areas

  • Pharmacology

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