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pubmed:abstractText |
The cytotoxicity of the antineoplastic drug hexadecylphosphocholine (HePC) was determined in a human monocytic tumor cell line, THP1, and in primary cultures of rat mesangial cells. Both cell types were susceptible to HePC toxicity, the concentrations producing 50% inhibition of cell viability (LD50 values) being 7 micrograms/ml for THP1 cells and 19 micrograms/ml for mesangial cells. The degree of toxicity was dependent on the culture conditions. In the absence of serum, HePC was highly toxic independent of cell proliferation. As a potential molecular mechanism, the effect of HePC on long-chain fatty acyl metabolism was investigated. HePC had no effect on fatty acid incorporation into cellular lipids or on release of fatty acids from lipid stores. The distribution of labeled fatty acids, however, was shifted from the phospholipid fraction to the triacylglycerol fraction. This effect was in accordance with an inhibition of the activity of the reacylating enzyme lysophosphatide acyltransferase. There was, however, no correlation between the interference with fatty acid distribution and HePC cytotoxicity in vitro. The data argue against interference with membrane fatty acid metabolism as a necessary prerequisite of HePC toxicity, the mechanism of which remains to be elucidated.
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