INHIBITION OF PHOSPHOLIPASE C-DELTA BY HEXADECYLPHOSPHORYLCHOLINE AND LYSOPHOSPHOLIPIDS WITH ANTITUMOR-ACTIVITY

The antineoplastic compound hexadecylphosphorylcholine (HPC) was shown to be a highly effective inhibitor of phospholipase C6 (PLCdelta1), with an 150 of about 30 nmol/mL (30 muM) in the presence and absence of 200 muM spermine. A number of lysophospholipids, of which HPC can be considered to be a structural analog, also inhibited PLC. Lysosphingomyelin, lysophosphatidylserine, and lysophosphatidylcholine exhibited Iso values of 15, 10, and 7 nmol/mL, respectively, in the presence of 200 muM spermine. The I50 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 PLCdelta1. 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.