Effects of hexadecylphosphocholine on membrane phospholipid metabolism in human tumour cells

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

“…These data contrast with those obtained with other cell lines such as Raji and KB cells, in which a pronounced decrease in the incorporation of [ 14 C]choline into PC was paralleled by an increase in the degradation of this phospholipid [32].…”

“…In a similar way, our results demonstrate that in the tumoral hepatic cell line HepG2, HePC hinders the incorporation of radiolabelled choline into PC, the endproduct of the CDP-choline pathway. This reduction in the incorporation of choline was not due to any alteration in its uptake by the cells, a finding which agrees with that of Geilen et al [31] working with MDCK cells, but it does go against observations made by other researchers working with neuronal cells [16] and KB and Raji cells [32], in which the authors showed that APC did in fact interfere with the uptake of choline into the cell, leading to a decrease in PC biosynthesis. In the present work we exposed the cells to HePC between 5 min and 6 h and did not observe any change in the uptake of choline, thus demonstrating that in this cell line at least the mechanism via which HePC acts is unrelated to the availability of intracellular choline.…”

The influence of 1-β- D-arabinofuranosylcytosine on the metabolism of phosphatidylcholine in human leukemic HL 60 and Raji cells

“…LysoPC is readily incorporated in the cellular membranes and rapidly acylated to PC. 29,31 The increase of the membrane concentration of PC correlated well with a substantial protection of the cells from Ara-C-induced cell death. Similar experiments with other myeloid and lymphatic cell lines and primary AML blasts from patients proved that the antagonism of Ara-C toxicity by lysoPC seemed to be a general phenomenon.…”

“…33 One of the pleiotropic effects of this compound is the reduction of PC content by inhibition of the CTP:phosphocholine cytidylyltransferase, 28 the same enzyme that also seems to be inhibited by Ara-CTP, 20 and by enhanced transfer of a phosphocholine group from PC to sphingomyeline. 29 Combination treatment of Ara-C and HePC showed pronounced synergistic cytotoxic effects in HL 60 and Raji cells. It has to be stressed, however, that Raji cells tolerated far higher doses of both compounds, indicating that to bypass a decrease of membrane PC, maybe by alternative PC synthesis pathways over the above mentioned PS-shunt, could be a possible common mechanism of resistance towards Ara-C and HePC.…”

“…HePC by itself interferes with cellular PC metabolism by inhibition of CTP:phosphocholine cytidylyltransferase 28 and enhancement of PC degradation via a transfer of a phosphocholine group on SM. 29 As summarized in Table 4, after 48 h of culture the cells showed different susceptibility towards Ara-C and HePC, the Raji cell line being the more resistant towards both substances. A combination treatment lead to a significant additive cytotoxic effect in both cell lines.…”