Wieder T, Haase A, Geilen C C, Orfanos C E
Haut- und Poliklinik, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Lipids. 1995 May;30(5):389-93. doi: 10.1007/BF02536296.
The concentration-dependent effects of two different synthetic phospholipids on cell proliferation and phosphatidylcholine biosynthesis were compared in Madin-Darby canine kidney (MDCK) cells. The alkyllysophospholipid 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine and the alkylphosphocholine, hexadecylphosphocholine, inhibited cell proliferation with half-inhibitory concentrations (IC50) of 75 and 135 mumol/L, respectively. The agents also inhibited phosphatidylcholine biosynthesis in confluent and proliferating MDCK cells. The IC50 of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine was 40 mumol/L in confluent cells and 20 mumol/L in proliferating cells, whereas the IC50 of hexadecylphosphocholine was higher in both experimental systems (67 mumol/L in confluent cells and 40 mumol/L in proliferating cells). Further experiments revealed that the effect of both agents on phosphatidylcholine biosynthesis was reversible and that the inhibition was mediated by translocation of the rate-limiting enzyme of this pathway, CTP:phosphocholine cytidylyltransferase (EC 2.7.7.15), from membranes to the cytosol, where it is inactive. The present findings suggest that the inhibition of phosphatidylcholine biosynthesis by both synthetic phospholipids might be related, in part, to their antiproliferative effects.
在Madin-Darby犬肾（MDCK）细胞中比较了两种不同合成磷脂对细胞增殖和磷脂酰胆碱生物合成的浓度依赖性影响。烷基溶血磷脂1-O-十八烷基-2-O-甲基-sn-甘油-3-磷酸胆碱和烷基磷酸胆碱十六烷基磷酸胆碱分别以75和135μmol/L的半抑制浓度（IC50）抑制细胞增殖。这些试剂还抑制汇合和增殖的MDCK细胞中的磷脂酰胆碱生物合成。1-O-十八烷基-2-O-甲基-sn-甘油-3-磷酸胆碱在汇合细胞中的IC50为40μmol/L，在增殖细胞中为20μmol/L，而十六烷基磷酸胆碱在两个实验系统中的IC50均较高（汇合细胞中为67μmol/L，增殖细胞中为40μmol/L）。进一步的实验表明，两种试剂对磷脂酰胆碱生物合成的作用是可逆的，并且抑制作用是由该途径的限速酶CTP：磷酸胆碱胞苷转移酶（EC 2.7.7.15）从膜转移到胞质溶胶介导的，在胞质溶胶中它是无活性的。目前的研究结果表明，两种合成磷脂对磷脂酰胆碱生物合成的抑制作用可能部分与其抗增殖作用有关。
