Induction of differentiation of human myeloid leukemia HL-60 cells by novel nonphosphorus alkyl ether lipids.
We synthesized a new series of nonphosphorus alkyl ether glycerolipids, in which the 2-acetyl group of platelet-activating factor was replaced by a pyrimidin-2-yl group and the 3-phosphocholine portion by an omega-(substituted ammonio)ethoxyethyl side-chain including omega-thiazolio-, imidazolio- and pyridinio groups with or without a carboxyl substituent, respectively (compound I-XI). Their effects on cell proliferation and differentiation of human myeloid leukemia HL-60 cells were examined. Incubation of HL-60 cells with these cationic and zwitterionic alkyl ether lipids inhibited proliferation of HL-60 cells with IC50 values ranging from 10 to 500 ng/mL. The cells were induced by the lipids to differentiate into morphologically and functionally mature granulocytes. Among the compounds we tested, 1-octadecyl-2-pyrimidinyl-3-[3-(5- carboxylatepentyl)imidazolioethoxyethyl]glycerol (compound I) was the most effective in inducing differentiation of HL-60 cells. Compound I showed on a molar basis, an inhibitory effect on the leukemic cells over 50 times greater than did 2-(2-dodecyloxyethoxy)ethyl 2-pyridinio-ethyl phosphate, the antileukemic alkyl ether phospholipid.
Honma
Y
Y
Department of Chemotherapy, Saitama Cancer Center Research Institute, Japan.
Kasukabe
T
T
Hozumi
M
M
Akimoto
H
H
Nomura
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004790:Enzyme Induction; D005995:Glyceryl Ethers / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007938:Leukemia; D015473:Leukemia, Promyelocytic, Acute; D015394:Molecular Structure; D009113:Muramidase / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005995:Glyceryl Ethers; D009113:Muramidase