EARLY-STAGE MONITORING OF MILTEFOSINE INDUCED APOPTOSIS IN KB CELLS BY MULTINUCLEAR NMR-SPECTROSCOPY

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 mechan ism is still unclear. Miltefosine induces apoptosis in human epithelia l KB cells, but slows down only proliferation in rat C6 glioma cells. NMR spectroscopy on lipid extracts reveals increased diacylglycerol an d triacylglycerol biosynthesis in KB cells prior to DNA fragmentation indicating a CTP:phosphocholine-cytidylyltransferase (CT) inhibition b y the drug. Although C6 cells were morphologically affected by alterat ions in phospholipid composition and metabolism by a long term treatme nt (23 days) with the drug, no persistent diacylglycerol increase is o bserved.