Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy

Shinji Miwa, Shuuya Yano, Yasunori Tome, Naotoshi Sugimoto, Yukihiko Hiroshima, Fuminari Uehara, Sumiyuki Mii, Hiroaki Kimura, Katsuhiro Hayashi, Elena V. Efimova, Toshiyoshi Fujiwara, Hiroyuki Tsuchiya, Robert M. Hoffman

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Caffeine enhances the effect of certain anticancer drugs, but the mechanism of modulation is poorly understood. In this study, modulation of cisplatinum efficacy induced by caffeine was visualized at the subcellular level by real-time fluorescent-protein imaging. Mitotic and apoptotic changes were observed by imaging 143B human osteosarcoma dual-color cells, in which GFP is expressed in the nucleus and RFP is expressed in the cytoplasm. Modulation of the cell cycle was imaged using time-lapse imaging of HeLa cells expressing a fluorescent ubiquitination-based cell cycle indicator (FUCCI) in the nucleus. Clonogenic assays showed that caffeine increased the inhibition by cisplatinum on cell proliferation. Subcellular imaging demonstrated that cisplatinum decreased mitosis and induced apoptosis in 143B cells. The combination of cisplatinum and caffeine enhanced mitosis and subsequently increased apoptosis. Time-lapse imaging showed that cisplatinum strongly induced cell-cycle arrest in the S/G2 phase in HeLa-FUCCI cells. Caffeine overcame the cell-cycle arrest induced by cisplatinum, thereby increasing its efficacy, since cisplatinum is ineffective against quiescent cells. The data in this report indicate that caffeine modulates the cell cycle in cancer cells, thereby enhancing efficacy of cell-cycle-dependent anticancer drugs such as cisplatinum.

Original languageEnglish
Pages (from-to)2454-2460
Number of pages7
JournalJournal of Cellular Biochemistry
Volume114
Issue number11
DOIs
Publication statusPublished - Nov 2013

Fingerprint

Optical Imaging
Caffeine
Mitosis
Cell Cycle
Color
Fluorescence
Cells
Apoptosis
Imaging techniques
Time-Lapse Imaging
Ubiquitination
Cell Cycle Checkpoints
Modulation
G2 Phase
Osteosarcoma
S Phase
HeLa Cells
Pharmaceutical Preparations
Cell proliferation
Cytoplasm

Keywords

  • Apoptosis
  • Caffeine
  • Cell Cycle
  • Cisplatinum
  • Fluorescence Imaging
  • Fucci
  • Gfp
  • Mitosis
  • Modulation
  • Osteosarcoma
  • Rfp

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy. / Miwa, Shinji; Yano, Shuuya; Tome, Yasunori; Sugimoto, Naotoshi; Hiroshima, Yukihiko; Uehara, Fuminari; Mii, Sumiyuki; Kimura, Hiroaki; Hayashi, Katsuhiro; Efimova, Elena V.; Fujiwara, Toshiyoshi; Tsuchiya, Hiroyuki; Hoffman, Robert M.

In: Journal of Cellular Biochemistry, Vol. 114, No. 11, 11.2013, p. 2454-2460.

Research output: Contribution to journalArticle

Miwa, S, Yano, S, Tome, Y, Sugimoto, N, Hiroshima, Y, Uehara, F, Mii, S, Kimura, H, Hayashi, K, Efimova, EV, Fujiwara, T, Tsuchiya, H & Hoffman, RM 2013, 'Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy', Journal of Cellular Biochemistry, vol. 114, no. 11, pp. 2454-2460. https://doi.org/10.1002/jcb.24593
Miwa, Shinji ; Yano, Shuuya ; Tome, Yasunori ; Sugimoto, Naotoshi ; Hiroshima, Yukihiko ; Uehara, Fuminari ; Mii, Sumiyuki ; Kimura, Hiroaki ; Hayashi, Katsuhiro ; Efimova, Elena V. ; Fujiwara, Toshiyoshi ; Tsuchiya, Hiroyuki ; Hoffman, Robert M. / Dynamic color-coded fluorescence imaging of the cell-cycle phase, mitosis, and apoptosis demonstrates how caffeine modulates cisplatinum efficacy. In: Journal of Cellular Biochemistry. 2013 ; Vol. 114, No. 11. pp. 2454-2460.
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