title: Tumor-targeting Salmonella typhimurium A1-R decoys quiescent cancer cells to cycle as visualized by FUCCI imaging and become sensitive to chemotherapy.
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.
authors.affiliation: a AntiCancer, Inc. ; San Diego , CA USA.
authors.forename: Shuya
authors.initials: S
authors.lastname: Yano
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.forename: Fuminari
authors.initials: F
authors.lastname: Uehara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tazawa
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006801:Humans; D007399:Interphase; D051379:Mice; D008819:Mice, Nude; D012486:Salmonella typhimurium / Q000502:physiology*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D059008:Time-Lapse Imaging; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents
keywords: FUCCI; GFP, RFP, imaging; S. typhimurium A1-R; Salmonella typhimurium; cell cycle; chemotherapy; decoy; fluorescence ubiquitination-based cell cycle indicator; S. typhimurium; tumor-targeting bacteria