Selective methioninase-induced trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity

Shuya Yano, Shukuan Li, Qinghong Han, Yuying Tan, Michael Bouvet, Toshiyoshi Fujiwara, Robert M. Hoffman

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

A major impediment to the response of tumors to chemotherapy is that the large majority of cancer cells within a tumor are quiescent in G0/G1, where cancer cells are resistant to chemotherapy. To attempt to solve this problem of quiescent cells in a tumor, cancer cells were treated with recombinant methioninase (rMETase), which selectively traps cancer cells in S/G2. The cell cycle phase of the cancer cells was visualized with the fluorescence ubiquitination cell cycle indicator (FUCCI). At the time of rMETase-induced S/G2-phase blockage, identified by the cancer cells' green fluorescence by FUCCI imaging, the cancer cells were administered S/G2-dependent chemotherapy drugs, which interact with DNA or block DNA synthesis such as doxorubicin, cisplatin, or 5-fluorouracil. Treatment of cancer cells with drugs only, without rMETase-induced S/G2 phase blockage, led to the majority of the cancer-cell population being blocked in G0/G1 phase, identified by the cancer cells becoming red fluorescent in the FUCCI system. The G0/G1 blocked cells were resistant to the chemotherapy. In contrast, trapping of cancer cells in S/G2 phase by rMETase treatment followed by FUCCI-imaging-guided chemotherapy was highly effective in killing the cancer cells.

Original languageEnglish
Pages (from-to)8729-8736
Number of pages8
JournalOncotarget
Volume5
Issue number18
DOIs
Publication statusPublished - Jan 1 2014

Keywords

  • Cell cycle
  • Chemotherapy
  • FUCCI
  • HeLa cells
  • Imaging
  • MCF-7 cells
  • Recombinant methioninase
  • S/G phase block
  • rMETase

ASJC Scopus subject areas

  • Oncology

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