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Investigations on the apoptotic effects of hexadecylphosphocholine on resistant and non-resistant cells monitored by NMR spectroscopy.

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Engelmann J, Floegel U, Pfeuffer,  J
Department Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Zitation

Henke, J., Engelmann J, Floegel U, Pfeuffer, J., Kutscher B, Noessner G, Engel J, Voegeli, R., & Leibfritz, D. (1998). Investigations on the apoptotic effects of hexadecylphosphocholine on resistant and non-resistant cells monitored by NMR spectroscopy. Drugs of Today, 34 (Suppl. F), 37-50.


Zusammenfassung
The alkylphosphocholine miltefosine (hexadecylphosphocholine, HPC) has antineoplastic potential in vivo and in vitro. Its mode of action is mediated via the cell membrane, but the mechanism is still unclear. In this study it was found that the use of various nuclear magnetic resonance (NMR) spectroscopic methods (diffusion-weighted 1H- and 31P-NMR spectroscopy on viable cells, multinuclear NMR spectroscopy on lipid extracts) revealed metabolic and morphologic changes in HPC treated tumor cells. Miltefosine (up to 100 µM) was able to induce apoptosis in human epithelial KB cells, whereas in a resistant subline of this cell line (KBres) no such effect can be observed. In both cell lines necrosis took place, if they have been treated with high concentrations of HPC ( 200 µM). Apoptotic cells decrease in cell volume, whereas cells swell under necrotic conditions. An early effect of HPC treatment in KB and KBres was an increase of the neutral lipids triacylglycerol and diacylglycerol associated with changes of the intracellular signal transduction by the latter. If apoptosis was induced, an increased fatty acid biosynthesis was observed. This effect seems to be a specific marker of apoptosis in KB cells.