Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time fucci imaging

Shinji Miwa, Shuya Yano, Hiroaki Kimura, Mako Yamamoto, Makoto Toneri, Yasunori Matsumoto, Fuminari Uehara, Yukihiko Hiroshima, Takashi Murakami, Katsuhiro Hayashi, Norio Yamamoto, Michael Bouvet, Toshiyoshi Fujiwara, Hiroyuki Tsuchiya, Robert M. Hoffman

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Essentially every population of cancer cells within a tumor is heterogeneous, especially with regard to chemosensitivity and resistance. In the present study, we utilized the fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging system to investigate the correlation between cell-cycle behavior and apoptosis after treatment of cancer cells with chemotherapeutic drugs. HeLa cells expressing FUCCI were treated with doxorubicin (DOX) (5 mM) or cisplatinum (CDDP) (5 mM) for 3 h. Cell-cycle progression and apoptosis were monitored by time-lapse FUCCI imaging for 72 h. Time-lapse FUCCI imaging demonstrated that both DOX and CDDP could induce cell cycle arrest in S/G2/M in almost all the cells, but a subpopulation of the cells could escape the block and undergo mitosis. The subpopulation which went through mitosis subsequently underwent apoptosis, while the cells arrested in S/G2/M survived. The present results demonstrate that chemoresistant cells can be readily identified in a heterogeneous population of cancer cells by S/G2/M arrest, which can serve in future studies as a visible target for novel agents that kill cell-cycle-arrested cells.

Original languageEnglish
Pages (from-to)621-629
Number of pages9
JournalCell Cycle
Volume14
Issue number4
DOIs
Publication statusPublished - Feb 15 2015

Keywords

  • Cancer
  • Cell cycle
  • Chemoresistance
  • Chemosensitivity
  • Cisplatinum
  • Doxorubicin
  • FUCCI
  • GFP
  • HeLa
  • RFP
  • Time-lapse imaging
  • Tumor heterogeneity

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Miwa, S., Yano, S., Kimura, H., Yamamoto, M., Toneri, M., Matsumoto, Y., Uehara, F., Hiroshima, Y., Murakami, T., Hayashi, K., Yamamoto, N., Bouvet, M., Fujiwara, T., Tsuchiya, H., & Hoffman, R. M. (2015). Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time fucci imaging. Cell Cycle, 14(4), 621-629. https://doi.org/10.4161/15384101.2014.991604