Tumor-targeting salmonella typhimurium A1-R decoys quiescent cancer cells to cycle as visualized by FUCCI imaging and become sensitive to chemotherapy

Shuya Yano, Yong Zhang, Ming Zhao, Yukihiko Hiroshima, Shinji Miwa, Fuminari Uehara, Hiroyuki Kishimoto, Hiroshi Tazawa, Michael Bouvet, Toshiyoshi Fujiwara, Robert Hoffman

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Quiescent cancer cells are resistant to cytotoxic agents which target only proliferating cancer cells. Time-lapse imaging demonstrated that tumor-targeting Salmonella typhimurium A1-R (A1-R) decoyed cancer cells in monolayer culture and in tumor spheres to cycle from G0/G1 to S/G2/M, as demonstrated by fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging. A1-R infection of FUCCI-expressing subcutaneous tumors growing in nude mice also decoyed quiescent cancer cells, which were the majority of the cells in the tumors, to cycle from G0/G1 to S/G2/M, thereby making them sensitive to cytotoxic agents. The combination of A1-R and cisplatinum or paclitaxel reduced tumor size compared with A1-R monotherapy or cisplatinum or paclitaxel alone. The results of this study demonstrate that A1-R can decoy quiescent cancer cells to cycle to S/G2/M and sensitize them to cytotoxic chemotherapy. These results suggest a new paradigm of bacterial-decoy chemotherapy of cancer.

Original languageEnglish
Pages (from-to)3958-3963
Number of pages6
JournalCell Cycle
Volume13
Issue number24
DOIs
Publication statusPublished - Dec 15 2014

Keywords

  • Cell cycle
  • Chemotherapy
  • Decoy
  • FUCCI
  • GFP
  • Imaging
  • RFP
  • S. typhimurium A1-R
  • Tumor-targeting bacteria

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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