Selective destruction of human leukemic cells by alkyl-lysophospholipids.

Abstract

Abstract The effect of synthetic lysophospholipid analogs on the proliferation of human leukemic cells was studied in vitro. Cells from patients with various forms of leukemia were cultivated in the presence of nine different but chemically closely related lysophospholipids. Alkyl-lysophospholipid analogs were found to cause progressive killing of the leukemic cells over a period of 72 to 96 hr. This cytotoxic effect was dependent on the presence of the ether-linked aliphatic side chain in sn-1 of the glycerol molecule as well as on substitution of the hydroxy group in the sn-2 position. All lysophospholipid analogs that have an acyl bond in sn-1 were ineffective. The viability and replication of normal human cells either were not affected or were affected to a much lesser extent by the same alkyl-lysophospholipids. Tracer studies with labeled compounds indicate that surface activity is not the cause of the observed cytotoxicity but that the metabolic fate of the substances has to be considered. The data suggest that the absence or relative lack of an alkyl cleavage enzyme in leukemic cells is primarily responsible for the observed cytotoxicity. After the lysophospholipids have been adsorbed from lipoproteins of the serum onto the cellular membrane, the stable alkyl-lysophospholipid analogs interfere apparently with the phospholipid metabolism of the neoplastic cells.