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.