The effect of two synthetic phospholipids on cell proliferation and phosphatidylcholine biosynthesis in Madin-Darby canine kidney cells.
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.
Wieder
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T
Haut- und Poliklinik, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
Haase
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A
Geilen
C C
CC
Orfanos
C E
CE
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D019916:Choline-Phosphate Cytidylyltransferase; D004285:Dogs; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010742:Phospholipid Ethers / Q000138:chemical synthesis / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D000970:Antineoplastic Agents; D010713:Phosphatidylcholines; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; C026659:edelfosine; C039128:miltefosine; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase