Inhibition of Proliferation and Induction of Differentiation of Human and Mouse Myeloid Leukemia Cells by New Ethyleneglycol-type Nonphosphorus Alkyl Ether Lipids

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Abstract
A variety of ethyleneglycol-type nonphosphorus alkyl either lipids, either derivatives of diethylene-glycol in which the two hydroxyl groups were substituted with long chain alkyl and quaternary ammonioalkyl groups, were synthesized and their effects on proliferation and differentiation of cultured human (HL-60) and mouse (M1) myeloid leukemia cells were studied. Incubation with these compounds inhibited the cellular proliferation, and cells differentiated into morphologically and functionally mature granulocytes. Of the compounds tested, 1-[2-[2-octadecycloxy)ethoxy]ethoxy]-butylpyridinium mesylate (EG-6) was the most effective in inducing differentiation of HL-60 cells. Almost maximal indiction of differentiation and inhibition of growth of HL-60 cells on day 6 were observed when the cells were treated with EG-6 1 for day and then cultured without EG-6 for a further 5 days. The inhibitory effect of EG-6 on the leukemic cells was over 100 times more than that of 2- [2-(dodecyloxy)ethoxy]ethyl 2-pyridinioethyl phosphate, a potent antileukemic either phospholipid.