Arecoline arrests cells at prometaphase by deregulating mitotic spindle assembly and spindle assembly checkpoint: Implication for carcinogenesis

Yu Chu Wang, Yi Shan Tsai, Jau Ling Huang, Ka Wo Lee, Ching Chuan Kuo, Chung Sheng Wang, A. Mei Huang, Jang Yang Chang, Yuh Jyh Jong, Chang Shen Lin

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


One apparent feature of cancerous cells is genomic instability, which may include various types of chromosomal aberrations, such as translocation, aneuploidy, and the presence of micronuclei inside the cells. Mutagenic factors that promote the emergence of genomic instability are recognized as risk factors for the development of human malignancies. In Asia, betel quid (BQ) chewing is one of such risk factors for oral cancer. Areca nut is an essential constitute of BQ and is declared as a group I carcinogen by the International Agency for Research on Cancer. However, the molecular and cellular mechanisms regarding the carcinogenicity of areca nut are not fully explored. Here we reported that arecoline, a major alkaloid of areca nut, could arrest cells at prometaphase with large amounts of misaligned chromosomes. This prometaphase arrest was evidenced by condensed chromosome pattern, increased histone H3 phosphorylation, and accumulation of mitotic proteins, including aurora A and cyclin B1. To investigate the molecular mechanisms accounting for arecoline-induced prometaphase arrest, we found that arecoline could stabilize mitotic spindle assembly, which led to distorted organization of mitotic spindles, misalignment of chromosomes, and up-regulation of spindle assembly checkpoint (SAC) genes. The SAC proteins BubR1 and Mps1 were differentially modified between the cells treated with arecoline and nocodazole. This together with aurora A overexpression suggested that SAC might be partly suppressed by arecoline. As a result, the arecoline-exposed cells might produce progeny that contained various chromosomal aberrations and exhibited genomic instability.

Original languageEnglish
Pages (from-to)255-262
Number of pages8
JournalOral Oncology
Issue number4
Publication statusPublished - Apr 2010
Externally publishedYes


  • Arecoline
  • Betel quid
  • Chromosomal aberrations
  • Genomic instability
  • Mitotic arrest
  • Spindle assembly checkpoint

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research


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