EFFECTS OF HEXADECYLPHOSPHOCHOLINE ON FATTY-ACID METABOLISM - RELATION TO CYTOXICITY

The cytotoxicity of the antineoplastic drug hexadecylphosphocholine (H ePC) was determined in a human monocytic tumor cell line, THP1, and in primary cultures of rat mesangial cells. Both cell types were suscept ible to HePC toxicity, the concentrations producing 50% inhibition of cell viability (LD(50) values) being 7 mu g/ml for THP1 cells and 19 m u g/ml for mesangial cells. The degree of toxicity was dependent on th e culture conditions. In the absence of serum, HePC was highly toxic i ndependent of cell proliferation. As a potential molecular mechanism, the effect of HePC on long-chain fatty acyl metabolism was investigate d. HePC had no effect on fatty acid incorporation into cellular lipids or on release of fatty acids from lipid stores. The distribution of l abeled fatty acids, however, was shifted from the phospholipid fractio n to the triacylglycerol fraction. This effect was in accordance with an inhibition of the activity of the reacylating enzyme lysophosphatid e acyltransferase. There was, however, no correlation between the inte rference with fatty acid distribution and HePC cytotoxicity in vitro. The data argue against interference with membrane fatty acid metabolis m as a necessary prerequisite of HePC toxicity, the mechanism of which remains to be elucidated.