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Correlation of Ether Lipid Content of Human Leukemia Cell Lines and Their Susceptibility to 1-O-Octadecyl-2-O-methyl-rac-glycero-3-phosphocholine¹

Department of Biochemistry, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103

A number of synthetic ether-linked phospholipids are selectively cytotoxic to neoplastic cells. However, the mechanisms underlying this selective cytotoxicity are not known. We have investigated the etherlipid content of HL-60 and K562 human leukemia cells in relation to their sensitivity to 1-O-alkyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH₃). HL-60 cells are much more sensitive than K562 cells to the cytotoxic effects of ET-18-OCH₃ and, at the same time, they contain nearly twice as much ether lipid as the more resistant K562 cells. These observations suggested a relation between the cellular ether-lipid content and sensitivity to ET-18-OCH₃. Further evidence linking these properties was obtained when the ether-lipid content of K562 cells was increased by incubating them in medium containing 1-O-hexadecyl-sn-glycerol. This supplementation not only increased the ether-lipid content of the cells but also increased their sensitivity to ET-18-OCH₃. The 50% inhibitory concentration for ET-18-OCH₃ decreased from 18.4 µM in the control cells to 9.83 µM in the supplemented cells.

¹ Supported by USPHS Grants CA 43297 and HL 26818.

² Recipient of Individual National Research Service Award DK 08059.

Received 6/10/88. Revised 4/25/89. Accepted 5/11/89.