Disturbance of phospholipid metabolism during the selective destruction of tumor cells induced by alkyl-lysophospholipids

Abstract

Alkyl-lysophospholipids inhibit the growth of Meth A sarcoma cells in vitro. In contrast, murine bone marrow macrophages are not sensitive to the destructive effect of these substances. Since alkyl-lysophospholipids are antimetabolites in the synthesis of 3-sn-phosphatidylcholine, tumor cell destruction can be correlated with the disturbance of this metabolism. A decreased synthesis of 3-sn-phosphatidylcholine is accompanied by an increased degradation of cellular 3-sn-phosphatidylcholine in the presence of alkyl-lysophospholipids. As a consequence, endogeneously formed lysophospholipid accumulates, although the lysophospholipase is found to be stimulated. This accumulation of endogeneous lysophospholipids might be due to the fact that a high percentage of these compounds contain an alkyl bond which cannot be split by a lysophospholipase. On the other hand, the reacylation of the formed lysophospholipids is partially blocked as the lysophosphatidylcholine acyltransferase is inhibited by the added alkyllysophospholipids. An accumulation of potentially cytotoxic lysophospholipids in tumor cells might be an additional factor in the tumor cell destruction by alkyl-lysophospholipids.