Cytotoxic effects of alkyl-lysophospholipids in human brain tumor cells.

The cytostatic activity of alkyl-lysophospholipids (ALP) was investigated in vitro with cells from 2 astrocytomas, 2 glioblastomas and a meningioma. In all lines the incorporation of [3H]thymidine into the tumor cells was inhibited by ALP. This effect was dependent on the ALP dose and incubation time. Incorporation rates were less than 5-10% of the control rates after an incubation time of more than 48 h with the ALP compound at a concentration of 20 micrograms/ml. 2-lysophosphatidylcholine, the ester-linked lysophospholipid, did not reveal any cytostatic effects. As a morphological criterion for severe cell damage, the trypan blue dye exclusion test was performed. Results were closely correlated with those of the thymidine incorporation inhibition assay. Further morphological evidence for actual damage of the tumor cell, caused by ALP incubation, was obtained by light microscopy of cytocentrifuge preparations and scanning electron microscopy. Membrane defects of tumor cells incubated with ALP were observed both in light and scanning electron microscopy, whereas untreated control cells remained intact. In cytocentrifuge smears of tumor cells, karyorrhexis occurred after 24 h of ALP treatment. After 48 h the cells looked almost completely damaged, and only fragments remained. Microvilli, blebs and ruffles, which indicate high surface activity and are characteristic morphological features of neoplastic astroglial cells in scanning electron microscopy, were severely disturbed by ALP incubation. Finally, the ability of tumor cells to adhere to glass and plastic surfaces was affected.