title: The antineoplastic ether lipid, s-phosphonate, selectively induces apoptosis in human leukemic cells and exhibits antiangiogenic and apoptotic activity on the chorioallantoic membrane of the chick embryo.
abstract: BACKGROUND
  We investigated the cytotoxic and antiangiogenic activity of the ether lipid, 2'-(trimethylammonio)ethyl 4-(hexadecyloxy)-3(S)-methoxybutane-phosphonate (termed s-phosphonate).
  
  
  METHODS
  Cytotoxicity was determined using an XTT bioassay. Apoptosis was measured by either DNA fragmentation or immunolabelling techniques. Angiogenesis was measured using the in vivo chorioallantoic membrane (CAM) of the chick embryo.
  
  
  RESULTS
  S-phosphonate was selectively cytotoxic towards the human leukemic cell lines, HL-60 and AML-14, whereas leukemic K-562 cells and the murine mast cell line, MC-9, were resistant to this agent at concentrations as high as 50 microM. This selectivity resulted from the induction of apoptosis (or programmed cell death) by s-phosphonate in HL-60 and AML-14 cells but not in resistant K-562 or MC-9 cells. S-phosphonate induced localized antiangiogenic effects and membrane thinning in the CAM. This concentration-dependent antiangiogenic effect was associated with apoptosis in the CAM as measured by DNA fragmentation in extracted CAM tissue. The localized areas of membrane thinning and antiangiogenesis on the CAM caused by s-phosphonate were also the only areas of the membrane in which apoptosis occurred.
  
  
  CONCLUSIONS
  We conclude that s-phosphonate selectively induces apoptosis in human leukemic cells and exhibits antiangiogenic and apoptotic activity on the CAM.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: J K
authors.initials: JK
authors.lastname: Jackson
authors.forename: H M
authors.initials: HM
authors.lastname: Burt
authors.forename: A M
authors.initials: AM
authors.lastname: Oktaba
authors.forename: W
authors.initials: W
authors.lastname: Hunter
authors.forename: M P
authors.initials: MP
authors.lastname: Scheid
authors.forename: F
authors.initials: F
authors.lastname: Mouhajir
authors.forename: R W
authors.initials: RW
authors.lastname: Lauener
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: H
authors.initials: H
authors.lastname: Salari
authors.forename: V
authors.initials: V
authors.lastname: Duronio
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000473:pathology*; D009389:Neovascularization, Pathologic; D063065:Organophosphonates; D010743:Phospholipids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D063065:Organophosphonates; D010743:Phospholipids; C079294:2'-(trimethylammonio)ethyl-4-(hexadecyloxy)-3-methoxybutane phosphonate