Fleer E A, Unger C, Kim D J, Eibl H
Max-Planck-Institut für biophysikalische Chemie, Abt. 140, Am Fassberg, Goettingen.
Lipids. 1987 Nov;22(11):856-61. doi: 10.1007/BF02535544.
The ether phospholipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (OM-GPC) is known to be a potent inhibitor of cell growth. Metabolic studies in both Raji and L1210 leukemic cells on OM-GPC, 3H-labeled in the methyl groups of the choline moiety, showed a (diacyl)-phosphatidylcholine as the only labeled metabolite. Since the formation of radiolabeled (diacyl)-phosphatidylcholine showed a direct correlation with cell death, we tested other lipid analogs. One of these compounds, hexadecylphosphocholine (He-PC), which was 3H-labeled in the methyl-choline groups, showed a formation of labeled (diacyl)-phosphatidylcholine similar to that found with OM-GPC. Again, there was a direct linear correlation between the formation of the labeled product and cell death. He-PC was found to be a potent cell toxin in in vitro experiments on cell cultures. However, analogs with an elongated phosphor to trimethylammonium distance showed no toxicity towards the cells in in vitro experiments. From the data, we conclude that the ether phospholipids are substrates for a phospholipase C or related enzyme. This substrate property may be responsible for the toxicity of the compounds in neoplastic cells.
醚磷脂1-O-十八烷基-2-O-甲基-rac-甘油-3-磷酸胆碱（OM-GPC）是一种已知的强效细胞生长抑制剂。在Raji和L1210白血病细胞中对胆碱部分甲基用3H标记的OM-GPC进行的代谢研究表明，（二酰基）-磷脂酰胆碱是唯一的标记代谢产物。由于放射性标记的（二酰基）-磷脂酰胆碱的形成与细胞死亡直接相关，我们测试了其他脂质类似物。其中一种化合物十六烷基磷脂胆碱（He-PC），其甲基胆碱基团用3H标记，显示出与OM-GPC类似的标记（二酰基）-磷脂酰胆碱的形成。同样，标记产物的形成与细胞死亡之间存在直接的线性关系。在细胞培养的体外实验中发现He-PC是一种强效细胞毒素。然而，磷到三甲基铵距离延长的类似物在体外实验中对细胞没有毒性。从这些数据中，我们得出结论，醚磷脂是磷脂酶C或相关酶的底物。这种底物特性可能是这些化合物对肿瘤细胞具有毒性的原因。
