Caffeine yields aneuploidy through asymmetrical cell division caused by misalignment of chromosomes

Yoko Katsuki, Shinichiro Nakada, Tetsuji Yokoyama, Issei Imoto, Johji Inazawa, Masayuki Nagasawa, Shuki Mizutani

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Aneuploidy has been implicated as an important step leading to various neoplasias. Although genetic factors that block aneuploidy have been the subject of intense interest, the impact of pharmacological and environmental substances on the development of aneuploidy has not been studied. Here, we show that caffeine induces aneuploidy through asymmetrical cell division. Mitotic exits of HeLa, U2OS, and primary fibroblast cells were significantly delayed by 10 mmol/L caffeine. Most caffeine-treated mitotic cells showed misalignment of chromosomes at the metaphase plates, and were arrested at prometaphase. Mitoticarrest deficient 2 (MAD2) depletion rescued the caffeine-induced delay of mitotic exit, indicating that caffeine-induced prolongation of mitosis was caused by activation of a MAD2-dependent spindle checkpoint. Enumeration of centromeres by fluorescence in situ hybridization revealed that cell division in the presence of caffeine was not symmetrical and resulted in aneuploid cell production. Most of these cells survived and underwent DNA synthesis. Our findings reveal a novel pharmacological effect of a high concentration of caffeine on genomic stability in dividing cells.

Original languageEnglish
Pages (from-to)1539-1545
Number of pages7
JournalCancer Science
Volume99
Issue number8
DOIs
Publication statusPublished - 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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