Inhibition of phospholipase cδ by hexadecylphosphorylcholine and lysophospholipids with antitumor activity

Abstract The antineoplastic compound hexadecylphosphorylcholine (HPC) was shown to be a highly effective inhibitor of phospholipase Cδ (PLCδ 1 ), with an I 50 of about 30 nmol mL (30μM) in the presence and absence of 200μM spermine. A number of lysophospholipids, of which HPC can be considered to be a structural analog, also inhibited PLC. Lysosphingomyelin, lysophosphatidylserine, and lysophosphatidylcholine exhibited I 50 values of 15,10, and 7 nmol mL , respectively, in the presence of 200 μM spermine. The 150 values were increased to 21–53 nmol mL in the absence of spermine. N , N -Dimethylsphingosine and N , N , N -trimethylsphingosine, which inhibit the metastatic potential of human and murine tumor cells, were weak activators of PLCδ 1 . It is postulated that HPC is more effective as an antineoplastic agent than lysophospholipids because HPC is metabolized slowly, while the lysophospholipids are metabolized rapidly in vivo .