title: Imaging the Different Mechanisms of Prostate Cancer Cell-killing by Tumor-targeting Salmonella typhimurium A1-R.
abstract: OBJECTIVE
  We previously developed a genetically-modified bacterial strain of Salmonella typhimurium, auxotrophic for leucine and arginine, which also expresses green fluorescent protein (GFP), termed S. typhimurium A1-R. S. typhimurium A1-R was found to be effective against metastatic human prostate, breast, pancreatic, cervical and ovarian cancer, as well as osteosarcoma, fibrosarcoma and glioma, in clinically relevant nude mouse models.
  
  
  METHODS
  To understand the tumor cell-killing mechanism of S. typhimurium A1-R-GFP, we studied the interaction of S. typhimurium A1-R-GFP with three different prostate cancer cell lines in vitro. S. typhimurium-GFP invasion, proliferation, and means of killing in three different human prostate cancer cell lines were visualized by confocal fluorescence microscopy with the Olympus FV1000.
  
  
  RESULTS
  We found that S. typhimurium A1-R-induced cancer-cell death had different mechanisms in different prostate cancer cell lines, occurring through apoptosis and necrosis in the PC-3 prostate cancer cell line, and by cell bursting in the LNCaP and DU-145 prostate cancer cell lines. The time required for S. typhimurium A1-R-GFP to kill the majority of cancer cells varied from line to line, ranging from 2 hours to 48 hours.
  
  
  CONCLUSIONS
  Understanding the various mechanisms of cancer-cell killing by S. typhimurium A1-R will be important for its use as a general therapeutic for cancer.
authors.affiliation: AntiCancer Inc., San Diego, CA, U.S.A. Faculty of Physics and Mechatronics, Dept. of Biophotonics and Laser Technology Saarland University, Saarbruecken, Germany.
authors.forename: Aisada
authors.initials: A
authors.lastname: Uchugonova
authors.affiliation: AntiCancer Inc., San Diego, CA, U.S.A.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: AntiCancer Inc., San Diego, CA, U.S.A.
authors.forename: Renee
authors.initials: R
authors.lastname: Salz
authors.affiliation: AntiCancer Inc., San Diego, CA, U.S.A.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: AntiCancer Inc., San Diego, CA, U.S.A.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suetsugu
authors.affiliation: AntiCancer Inc., San Diego, CA, U.S.A.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Faculty of Physics and Mechatronics, Dept. of Biophotonics and Laser Technology Saarland University, Saarbruecken, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Koenig
authors.affiliation: AntiCancer Inc., San Diego, CA, U.S.A. Department of Surgery, University of California, San Diego, CA, U.S.A. all@anticancer.com.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.affiliation: AntiCancer Inc., San Diego, CA, U.S.A.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
mesh_terms: D001691:Biological Therapy; D016923:Cell Death; D045744:Cell Line, Tumor; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D012486:Salmonella typhimurium / Q000145:classification / Q000235:genetics
chemical_list: D049452:Green Fluorescent Proteins
keywords: DU-145; GFP; LNCaP; PC-3; RFP; Salmonella typhimurium A1-R; apoptosis; cell burst; cell line; necrosis; prostate cancer; tumor targeting