This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, X. Articles by Arthur, G. Search for Related Content PubMed PubMed Citation Articles by Lu, X. Articles by Arthur, G.

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 Phospholipids¹

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

Proliferation of A427, a lung cancer cell line, was significantly decreased 10 h after incubation with 5 µg/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 µg/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. Our results indicated that a strict correlation did not exist between the quantity of the ALP accumulated and sensitivity to the compound.

¹ This work was supported by funds from the National Cancer Institute of Canada and a Medical Research Council Scholarship to G. A.

² To whom requests for reprints should be addressed, at Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada, R3E OW3.

Received 11/ 4/91. Accepted 3/ 9/92.

This article has been cited by other articles:

				C. Gajate, A. Santos-Beneit, M. Modolell, and F. Mollinedo Involvement of c-Jun NH2-Terminal Kinase Activation and c-Jun in the Induction of Apoptosis by the Ether Phospholipid 1-O-Octadecyl-2-O-methyl-rac-glycero-3-phosphocholine Mol. Pharmacol., April 1, 1998; 53(4): 602 - 612. [Abstract] [Full Text]