Cytotoxicity of Thioether-Lysophospholipids in Leukemias and Tumors of Human Origin

Thioether-lysophospholipids inhibited the in vitro incorporation of [³H]thymidine into blasts of 8 leukemias, lymphocytes of 3 chronic lymphocytic leukemias, and cells of 12 different solid tumors of human origin. This effect correlated with trypan blue dye exclusion, which was used to assess cell damage. Scanning electron microscopy revealed severe membrane destruction after incubation with thioether-lysophospholipids. Cytostatic and cytotoxic effects of thioether-lysophospholipids were dependent on dosage and incubation time. Destruction of leukemic blasts was completed with ⩾5 µg/ml after an incubation of ⩾48 hr, but 10 to 20 µg/ml were necessary in solid tumors. Ester-linked 2-lysophosphatidylcholine was ineffective in the same dose range, which points to the requirement of the alkyl moiety in S_N1 of the molecule for the antineoplastic properties of lysophospholipid analogues.