Pawelczyk T, Lowenstein J M
Graduate Department of Biochemistry, Brandeis University, Waltham, MA 02254.
Biochem Pharmacol. 1993 Jan 26;45(2):493-7. doi: 10.1016/0006-2952(93)90087-d.
The antineoplastic compound hexadecylphosphorylcholine (HPC) was shown to be a highly effective inhibitor of phospholipase C delta (PLC delta 1), with an I50 of about 30 nmol/mL (30 microM) in the presence and absence of 200 microM spermine. A number of lysophospholipids, of which HPC can be considered to be a structural analog, also inhibited PLC. Lysosphingomyelin, lysophosphatidylserine, and lysophosphatidylcholine exhibited I50 values of 15, 10, and 7 nmol/mL, respectively, in the presence of 200 microM 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 PLC delta 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.
抗肿瘤化合物十六烷基磷酰胆碱（HPC）被证明是磷脂酶Cδ（PLCδ1）的高效抑制剂，在存在和不存在200μM精胺的情况下，其半数抑制浓度（I50）约为30nmol/mL（30μM）。许多溶血磷脂（HPC可被视为其结构类似物）也能抑制PLC。在存在200μM精胺的情况下，溶血神经鞘磷脂、溶血磷脂酰丝氨酸和溶血磷脂酰胆碱的I50值分别为15、10和7nmol/mL。在不存在精胺的情况下，I50值增加到21 - 53nmol/mL。抑制人和鼠肿瘤细胞转移潜能的N，N - 二甲基鞘氨醇和N，N，N - 三甲基鞘氨醇是PLCδ1的弱激活剂。据推测，HPC作为抗肿瘤药物比溶血磷脂更有效，因为HPC代谢缓慢，而溶血磷脂在体内代谢迅速。
