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

Shinji Miwa, Shuuya 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

16 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

Fingerprint

Cell Cycle
Ubiquitination
Pharmaceutical Preparations
Population
Neoplasms
Fluorescence
Apoptosis
Mitosis
Doxorubicin
Cell Cycle Checkpoints
HeLa Cells

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time fucci imaging. / Miwa, Shinji; Yano, Shuuya; Kimura, Hiroaki; Yamamoto, Mako; Toneri, Makoto; Matsumoto, Yasunori; Uehara, Fuminari; Hiroshima, Yukihiko; Murakami, Takashi; Hayashi, Katsuhiro; Yamamoto, Norio; Bouvet, Michael; Fujiwara, Toshiyoshi; Tsuchiya, Hiroyuki; Hoffman, Robert M.

In: Cell Cycle, Vol. 14, No. 4, 15.02.2015, p. 621-629.

Research output: Contribution to journalArticle

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, RM 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, vol. 14, no. 4, pp. 621-629. https://doi.org/10.4161/15384101.2014.991604
Miwa, Shinji ; Yano, Shuuya ; Kimura, Hiroaki ; Yamamoto, Mako ; Toneri, Makoto ; Matsumoto, Yasunori ; Uehara, Fuminari ; Hiroshima, Yukihiko ; Murakami, Takashi ; Hayashi, Katsuhiro ; Yamamoto, Norio ; Bouvet, Michael ; Fujiwara, Toshiyoshi ; Tsuchiya, Hiroyuki ; Hoffman, Robert M. / Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time fucci imaging. In: Cell Cycle. 2015 ; Vol. 14, No. 4. pp. 621-629.
@article{8ac1fbdcec834a1897a756a9114c14f3,
title = "Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time fucci imaging",
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.",
keywords = "Cancer, Cell cycle, Chemoresistance, Chemosensitivity, Cisplatinum, Doxorubicin, FUCCI, GFP, HeLa, RFP, Time-lapse imaging, Tumor heterogeneity",
author = "Shinji Miwa and Shuuya Yano and Hiroaki Kimura and Mako Yamamoto and Makoto Toneri and Yasunori Matsumoto and Fuminari Uehara and Yukihiko Hiroshima and Takashi Murakami and Katsuhiro Hayashi and Norio Yamamoto and Michael Bouvet and Toshiyoshi Fujiwara and Hiroyuki Tsuchiya and Hoffman, {Robert M.}",
year = "2015",
month = "2",
day = "15",
doi = "10.4161/15384101.2014.991604",
language = "English",
volume = "14",
pages = "621--629",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "4",

}

TY - JOUR

T1 - Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time fucci imaging

AU - Miwa, Shinji

AU - Yano, Shuuya

AU - Kimura, Hiroaki

AU - Yamamoto, Mako

AU - Toneri, Makoto

AU - Matsumoto, Yasunori

AU - Uehara, Fuminari

AU - Hiroshima, Yukihiko

AU - Murakami, Takashi

AU - Hayashi, Katsuhiro

AU - Yamamoto, Norio

AU - Bouvet, Michael

AU - Fujiwara, Toshiyoshi

AU - Tsuchiya, Hiroyuki

AU - Hoffman, Robert M.

PY - 2015/2/15

Y1 - 2015/2/15

N2 - 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.

AB - 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.

KW - Cancer

KW - Cell cycle

KW - Chemoresistance

KW - Chemosensitivity

KW - Cisplatinum

KW - Doxorubicin

KW - FUCCI

KW - GFP

KW - HeLa

KW - RFP

KW - Time-lapse imaging

KW - Tumor heterogeneity

UR - http://www.scopus.com/inward/record.url?scp=84923613955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923613955&partnerID=8YFLogxK

U2 - 10.4161/15384101.2014.991604

DO - 10.4161/15384101.2014.991604

M3 - Article

VL - 14

SP - 621

EP - 629

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 4

ER -