Metabolism of alkyl lysophospholipid in epithelial cancer cell lines and inhibition of cell growth

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Abstract
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 μg OMG/mL (2.8 μM) 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 μg ET-18-OCH3/mL (9.6 μM). While 12 h incubation with 1 μg OMG/mL did not significantly inhibit the proliferation of MCF7 or A427 cells, incubation with 5 μg ET-18-OCH3/mL inhibited MCF7 and A427 growth by 90 and 15%, respectively. A549 cell growth was inhibited 10% by 1 μg OMG/mL, but not by 5 μg ET-18-OCH3/mL. Incubation of cells for 12 h with 5 μg OMG/mL (13.9 μM) 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.Key words: alkyllysophospholipid, metabolism, epithelial cancer cells, growth inhibition.

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