The differential susceptibility of A427 and A549 cell lines to the growth-inhibitory effects of ET-18-OCH3 does not correlate with the relative effects of the alkyl-lysophospholipid on the incorporation of fatty acids into cellular phospholipids.
Proliferation of A427, a lung cancer cell line, was significantly decreased 10 h after incubation with 5 micrograms/ml 1-O-octadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OCH3) while the proliferation of A549, another lung cancer cell line, was unaffected until 15 h after incubation with the alkyl-lysophospholipid (ALP). The relative sensitivity of cells to the antiproliferative effect of ET-18-OCH3 has been postulated to be due to the degree of inhibition of cellular acylation processes. We therefore investigated the effect of 5 micrograms/ml ET-18-OCH3 on the incorporation of fatty acids for up to 12 h, into A427 and A549 phospholipids. Significant changes observed in the incorporation of fatty acids into A427 phospholipids by the ALP were a decreased incorporation of oleic acid into PC after 8 h, an increased incorporation of linoleic acid into PE after 12 h, decreased incorporation of arachidonate into PE after 3 h, and increased incorporation into PA after 5 h. Although the above changes affected the distribution of newly esterified fatty acids in the phospholipids, there was no effect on the total quantity of label incorporated in the phospholipid fraction between the experimental and control cells after 12 h. Incubation of A549 cells with ET-18-OCH3 resulted in decreased esterification of oleic acid into PC, SM, and LPC after 5 h; decreased incorporation of linoleic into PE after 12 h; and a decreased incorporation of arachidonate into SM after 1.5 h. After 12 h incubation with ET-18-OCH3, changes in the distribution of radiolabeled fatty acids were observed in the quantitatively minor phospholipids, SM and LPC. A 20% decrease in the quantity of oleic acid incorporated into the phospholipids was observed in cells incubated with the ALP; however, no differences were observed in the quantity of linoleic or arachidonic acid incorporated into the phospholipids. The lack of common effects of the ALP on the incorporation of fatty acids into A427 and A549 phospholipids, coupled with the absence of changes that were more severe or manifested earlier in the more sensitive A427 cell line, suggests that the effect of ET-18-OCH3 on the acylation processes depends on the cell type and the fatty acid species and is unlikely to be responsible for the relative sensitivities of the cells to the compound. Radiolabeled ET-18-OCH3 was used to examine the correlation between the amount of the compound accumulated in A427, A549, MCF7, T84, and LS174T cells and the relative susceptibilities of the cells to the ALP.(ABSTRACT TRUNCATED AT 400 WORDS)
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Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
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D000215:Acylation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008246:Lysophospholipids / Q000378:metabolism; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005227:Fatty Acids; D008246:Lysophospholipids; D010742:Phospholipid Ethers; D010743:Phospholipids; C026659:edelfosine