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Induction of differentiation of human myeloid leukemia HL‐60 cells by novel nonphosphorus alkyl ether lipids
Author(s) -
Honma Yoshio,
Kasukabe Takashi,
Hozumi Motoo,
Akimoto Hiroshi,
Nomura Hiroaki
Publication year - 1991
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536583
Subject(s) - lipidology , clinical chemistry , myeloid leukemia , alkyl , ether , chemistry , leukemia , microbiology and biotechnology , biochemistry , organic chemistry , biology , cancer research , immunology
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 anω‐(substituted ammonio)ethoxyethyl side‐chain including ω‐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 IC 50 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‐carboxylatepenty)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‐pyridinioethyl phosphate, the antileukemic alkyl ether phospholipid.