Effect of 1-O-octadecyl-2-O-methyl-glycerophosphocholine on phosphatidylcholine and phosphatidylethanolamine synthesis in MCF-7 and A549 cells and its relationship to inhibition of cell proliferation.
The role of perturbation of lipid synthesis in the inhibition of cell proliferation by OctMeGroPCho was investigated with sensitive (MCF-7) and resilient (A549) cell lines. It inhibited de novo synthesis of phosphatidylcholine in both cells but increased triacylglycerol synthesis in A549 cells and phosphatidylethanolamine, phosphatidic acid and diacylglycerol synthesis in MCF-7 cells. The inhibition of synthesis of CDP-choline metabolites in MCF-7 cells and phosphatidylcholine biosynthetic enzyme activities in vitro by OctMeGroPCho suggests that direct inhibition of phosphocholine cytidylyltransferase may contribute to the observed inhibition of phosphatidylcholine synthesis. The activation of phosphoethanolamine cytidylyltransferase and ethanolamine phosphotransferase activities by OctMeGroPCho in vitro and increased production of CDP-ethanolamine suggest that stimulation of the above enzymes by OctMeGroPCho in the cells is responsible for the increased phosphatidylethanolamine synthesis. The apparent effect of OctMeGroPCho on intracellular lipid-metabolising enzymes is a strong indication that it may be widely distributed intracellularly and not just confined to the plasma membrane. The decrease in phosphatidylcholine synthesis by OctMeGroPCho in MCF-7 cells was prevented by co-incubation with oleic acid without any effect on the inhibition of cell growth. Although OctMeGroPCho resulted in similar decreases in phosphatidylcholine content in both cells, this did not affect the proliferation of A549 cells. The above results indicate that, although OctMeGroPCho has profound effects on lipid metabolism, these changes are not responsible for the inhibition of proliferation observed in MCF-7 cells.
Zhou
X
X
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Arthur
G
G
D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002794:Choline / Q000737:chemistry / Q000378:metabolism; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010714:Phosphatidylethanolamines / Q000096:biosynthesis*; D010742:Phospholipid Ethers / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014867:Water
D000970:Antineoplastic Agents; D004983:Ethanolamines; D009829:Oleic Acids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010742:Phospholipid Ethers; D014867:Water; C026659:edelfosine; D019301:Oleic Acid; D019856:Ethanolamine; D002794:Choline; D005990:Glycerol