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Arecoline induced cell cycle arrest, apoptosis, and cytotoxicity to human endothelial cells

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Abstract

Betel quid (BQ) chewing is a common oral habit in South Asia and Taiwan. BQ consumption may increase the risk of oral squamous cell carcinoma (OSCC), oral submucous fibrosis (OSF), and periodontitis as well as systemic diseases (atherosclerosis, hypertension, etc.). However, little is known about the toxic effect of BQ components on endothelial cells that play important roles for angiogenesis, carcinogenesis, tissue fibrosis, and cardiovascular diseases. EAhy 926 (EAHY) endothelial cells were exposed to arecoline, a major BQ alkaloid, for various time periods. Cytotoxicity was estimated by 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. The cell cycle distribution of EAHY cells residing in sub-G0/G1, G0/G1, S-, and G2/M phases was analyzed by propidium iodide staining of cellular DNA content and flow cytometry. Some EAHY cells retracted, became round-shaped in appearance, and even detached from the culture plate after exposure to higher concentrations of arecoline (> 0.4 mM). At concentrations of 0.4 and 0.8 mM, arecoline induced significant cytotoxicity to EAHY cells. At similar concentrations, arecoline induced G2/M cell cycle arrest and increased sub-G0/G1 population, a hallmark of apoptosis. Interestingly, prolonged exposure to arecoline (0.1 mM) for 12 and 21 days significantly suppressed the proliferation of EAHY cells, whereas EAHY cells showed adaptation and survived when exposed to 0.05 mM arecoline. These results suggest that BQ components may contribute to the pathogenesis of OSF and BQ chewing-related cardiovascular diseases via toxicity to oral or systemic endothelial cells, leading to impairment of vascular function. During BQ chewing, endothelial damage may be induced by areca nut components and associate with the pathogenesis of OSF, periodontitis, and cardiovascular diseases.

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Acknowledgements

This study is supported by a grant from National Science Council (NSC-97-2320-B-255-001-MY3), Taiwan, Republic of China and Chang Gung Memorial Hospital.

Conflicts of interest

The authors declare that there are no conflicts of interest for this submission.

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Authors and Affiliations

  1. Graduate Institute of Clinical Dentistry, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St, Beitou District, Taipei, Taiwan

    Shuei-Kuen Tseng, Cheng-Yao Su, Lin-Yang Chi & Ming-Lun Hsu

  2. Department of Dentistry, National Taiwan University Hospital, No 1, Chang-Te Street, Taipei, Taiwan

    Shuei-Kuen Tseng, Jenny Zwei-Ching Chang, Wan-Yu Tseng & Jiiang-Huei Jeng

  3. Laboratory of Dental Pharmacology, Toxicology & Pulp Biology, School of Dentistry, National Taiwan University Medical College, No 1, Chang-Te Street, Taipei, Taiwan

    Shuei-Kuen Tseng, Jenny Zwei-Ching Chang, Wan-Yu Tseng & Jiiang-Huei Jeng

  4. Biomedical Science Team, Chang Gung University of Science and Technology, Taoyuan, Taiwan

    Mei-Chi Chang

  5. Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan

    Sin-Yuet Yeung

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  1. Shuei-Kuen Tseng
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  6. Wan-Yu Tseng
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  8. Ming-Lun Hsu
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  9. Jiiang-Huei Jeng
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Correspondence to Ming-Lun Hsu or Jiiang-Huei Jeng.

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Mei-Chi Chang and Ming-Lun Hsu made an equal contribution to the first author.

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Tseng, SK., Chang, MC., Su, CY. et al. Arecoline induced cell cycle arrest, apoptosis, and cytotoxicity to human endothelial cells. Clin Oral Invest 16, 1267–1273 (2012). https://doi.org/10.1007/s00784-011-0604-1

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  • DOI: https://doi.org/10.1007/s00784-011-0604-1

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