Hexadecylphosphocholine inhibits phosphatidylcholine synthesis via both the methylation of phosphatidylethanolamine and CDP-choline pathways in HepG2 cells

Jiménez-López, José M.; Carrasco, Marı́a P.; Segovia, J.L.; Marco, Carmen

doi:10.1016/s1357-2725(03)00193-6

Cited by 17 publications

(17 citation statements)

References 39 publications

(30 reference statements)

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“…We have demonstrated that HePC can insert easily within a phospholipid monolayer, and we found a condensation effect with sterols (25). Moreover, HePC has been described to affect lipid metabolism in cancer cells (8,9,13,14) and in rat neurons (23).…”

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confidence: 55%

“…Inhibition of exogenous choline incorporation to PC (de novo synthesis) by HePC was also observed in a large panel of cell lines (8,9,13,23). This inhibitory effect is the consequence of an alteration in CTP-phosphocholinecytidylyltransferase activity in tumor cells (13,14,33,35).…”

Section: (34)mentioning

confidence: 77%

“…The effect of HePC on lipid metabolism in cancer cells has been described previously (13,14,33,35), and it was interesting to investigate whether HePC has similar effects on Leishmania. Therefore, we report in this paper on an analysis of Leishmania donovani membrane lipids in parasites stressed with HePC at sublethal concentrations in order to know whether the mechanism of action of HePC in Leishmania pro- …”

Section: Discussionmentioning

confidence: 92%

“…As we observed a simultaneous decrease in the amount of PC and an increase in the amount PE, the inhibition of N-methyltransferase activity by HePC in L. donovani promastigotes is probably the more convincing hypothesis. Moreover, such a phenomenon induced by HePC has already been observed in the protozoan parasite Trypanosoma cruzi (15), and the inhibition of N-methyltransferase activity by HePC has also been described in tumor cells (14).…”

Section: (34)mentioning

confidence: 83%

“…In tumor cells, the biosynthesis of this aminophospholipid, which is asymmetrically distributed within the membrane, is unaffected by HePC (14).…”

Section: (34)mentioning

confidence: 99%

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Miltefosine Affects Lipid Metabolism in Leishmania donovani Promastigotes

Rakotomanga

Blanc

Gaudin

et al. 2007

Antimicrob Agents Chemother

149

120

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Miltefosine (hexadecylphosphocholine [ HePC]) is the first orally active antileishmanial drug. Transient HePC treatment of Leishmania donovani promastigotes at 10 M significantly reduced the phosphatidylcholine content and enhanced the phosphatidylethanolamine (PE) content in parasite membranes, suggesting a partial inactivation of PE-N-methyltransferase. Phospholipase D activity did not seem to be affected by HePC. In addition, the enhancement of the lysophosphatidylcholine content could be ascribed to phospholipase A2 activation. Moreover, transient HePC treatment had no effect on the fatty acid alkyl chain length or the fatty acid unsaturation rate. Concerning sterols, we found a strong reduction of the C 24 alkylated sterol content, and the enhancement of the cholesterol content could be the result of the HePC condensation effect with sterols.

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confidence: 55%