title: Erufosine, an alkylphosphocholine, with differential toxicity to human cancer cells and bone marrow cells.
abstract: OBJECTIVE
  To investigate the activity and myeloprotective properties of erufosine, a novel alkylphosphocholine (APC), on human malignant cells and normal bone marrow cells.
  
  
  METHODS
  Human or mouse bone marrow cells were exposed to erufosine, miltefosine, perifosine, or edelfosine in CFU-GM assays. Human MDA-MB-231 breast carcinoma, Panc-1 pancreatic carcinoma, and RPMI8226 multiple myeloma cells were exposed to erufosine in colony formation assays. Colony formation of Panc-1 tumor cells and mouse bone marrow cells ex vivo were quantified following intravenous administration of erufosine to tumor-bearing mice. Western blotting methods were applied to human U87 glioblastoma cells exposed to erufosine to investigate Akt inhibition.
  
  
  RESULTS
  Erufosine was less toxic to human and mouse bone marrow cells than perifosine, miltefosine, and edelfosine and was equally toxic to human and mouse CFU-GM. The human cancer cells MDA-MB-231 breast, Panc-1 pancreatic, and RPMI8226 MM cells were more sensitive to erufosine in a colony formation assay than were human bone marrow cells generating an approximately tenfold differential in IC(90) values. Erufosine injected intravenously significantly reduced Panc-1 tumor cell colony formation ex vivo but not mouse bone marrow CFU-GM. Erufosine inhibited Akt phosphorylation in human U87 glioblastoma cells.
  
  
  CONCLUSIONS
  Erufosine offers potential as a novel therapeutic for cancer with a reduced toxicity profile to bone marrow cells compared with other agents in this class. Human cancer cells were more sensitive to erufosine than human or mouse bone marrow cells indicating a favorable therapeutic window for erufosine.
authors.affiliation: Genzyme Corporation, 49 New York Ave, Framingham, MA 01701-9322, USA. Rebecca.bagley@genzyme.com
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Bagley
authors.forename: Leslie
authors.initials: L
authors.lastname: Kurtzberg
authors.forename: Cecile
authors.initials: C
authors.lastname: Rouleau
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Teicher
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects*; D045744:Cell Line, Tumor; D003114:Colony-Forming Units Assay; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010755:Organophosphates / Q000494:pharmacology* / Q000633:toxicity; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology* / Q000633:toxicity; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D010755:Organophosphates; D000644:Quaternary Ammonium Compounds; C472787:erucylphospho-N,N,N-trimethylpropylammonium; D051057:Proto-Oncogene Proteins c-akt