Metabolism of alkyl lysophospholipid in epithelial cancer cell lines and inhibition of cell growth.
The mechanism of inhibition of cancer cell growth by alkyllysophospholipids is not known. We have investigated the metabolism of 1-O-octadecyl-2-O-methylglycerophosphocholine (ET-18-OCH3) in MCF7, A427, and A549 cell lines to determine whether there is a correlation between metabolism and sensitivity and whether the growth-inhibitory effects are due to ET-18-OCH3 or its metabolites. After 12 h incubation with ET-18-OCH3, less than 1.5% of ET-18-OCH3 taken up in the cells was converted to 1-O-octadecyl-2-O-methylglycerol (OMG). No correlation was observed between the extent of metabolism and sensitivity to the compound. Incubation of cells with 1 microgram OMG/mL (2.8 microM) for 12 h resulted in cellular quantities of OMG in MCF7, A427, and A549 that were, respectively, 8-, 5-, and 25-fold greater than those in cells incubated with 5 micrograms ET-18-OCH3/mL (9.6 microM). While 12 h incubation with 1 microgram OMG/mL did not significantly inhibit the proliferation of MCF7 or A427 cells, incubation with 5 micrograms ET-18-OCH3/mL inhibited MCF7 and A427 growth by 90 and 15%, respectively. A549 cell growth was inhibited 10% by 1 microgram OMG/mL, but not by 5 micrograms ET-18-OCH3/mL. Incubation of cells for 12 h with 5 micrograms OMG/mL (13.9 microM) inhibited the growth of all three cell lines. Our results indicate that both ET-18-OCH3 and OMG can inhibit cell growth but the low quantities of OMG produced from ET-18-OCH3 are not responsible for the observed inhibition of MCF7 and A427 cell growth.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
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D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005989:Glycerides / Q000378:metabolism; D005995:Glyceryl Ethers / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D010742:Phospholipid Ethers / Q000378:metabolism* / Q000494:pharmacology; D012878:Skin Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005989:Glycerides; D005995:Glyceryl Ethers; D010742:Phospholipid Ethers; C083471:1-O-octadecyl-2-O-methylglycerol; C026659:edelfosine