Correlation of ether lipid content of human leukemia cell lines and their susceptibility to 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine.
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 ether-lipid 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 microM in the control cells to 9.83 microM in the supplemented cells.
Chabot
M C
MC
Department of Biochemistry, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103.
Wykle
R L
RL
Modest
E J
EJ
Daniel
L W
LW
D000970:Antineoplastic Agents / Q000145:classification / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism*; D008563:Membrane Lipids / Q000145:classification / Q000378:metabolism; D010742:Phospholipid Ethers / Q000032:analysis* / Q000145:classification / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D008563:Membrane Lipids; D010742:Phospholipid Ethers; C026659:edelfosine