title: Early stage monitoring of miltefosine induced apoptosis in KB cells by multinuclear NMR spectroscopy.
abstract: Synthetic ether lipids, like miltefosine (hexadecylphosphocholine), an alkylphosphocholine, are antineoplastic agents in vitro and in vivo. Their mode of action is mediated via the cell membrane, but the mechanism is still unclear. Miltefosine induces apoptosis in human epithelial KB cells, but slows down only proliferation in rat C6 glioma cells. NMR spectroscopy on lipid extracts reveals increased diacylglycerol and triacyglycerol biosynthesis in KB cells prior to DNA fragmentation indicating a CTP:phosphocholine-cytidylyl-transferase (CT) inhibition by the drug. Although C6 cells were morphologically affected by alterations in phospholipid composition and metabolism by a long term treatment (23 days) with the drug, no persistent diacylglycerol increase is observed.
authors.affiliation: Institut für Organische Chemie, Universität Bremen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Engelmann
authors.forename: J
authors.initials: J
authors.lastname: Henke
authors.forename: W
authors.initials: W
authors.lastname: Willker
authors.forename: B
authors.initials: B
authors.lastname: Kutscher
authors.forename: G
authors.initials: G
authors.lastname: Nössner
authors.forename: J
authors.initials: J
authors.lastname: Engel
authors.forename: D
authors.initials: D
authors.lastname: Leibfritz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007624:KB Cells; D009682:Magnetic Resonance Spectroscopy; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D010767:Phosphorylcholine; C039128:miltefosine