Effect of alkyl-lysophospholipids on phosphatidylcholine biosynthesis in leukemic cell lines

Alkyl-lysophospholipids are ether analogues of lysophospholipids that have tumoricidal activity mediated through activation of macrophages or by direct effect on tumor cells by disturbance of phospholipid metabolism. The effect of racemic 1-octadecyl-2-methyl-sn-glycero-3 phosphocholine on phosphatidylcholine synthesis was investigated in sensitive (HL-60) and resistant (K-562) human leukemic cell lines. Radiolabeled lysophosphatidyl-choline, choline, and methionine incorporation into phosphatidylcholine was measured in intact cells exposed for 24 h to varying concentrations of the compound. In HL-60 cells, marked inhibition of phosphatidylcholine synthesis was demonstrated using lysophosphatidylcholine or choline as precursors, but no effect was observed on methionine incorporation. No effects were observed in K-562 cells. These investigations suggest that alkyl-lysophospholipids inhibit phosphatidylcholine synthesis via the acyltransferase reaction and from choline, but not from methionine.