Inhibition of proliferation and induction of differentiation of human and mouse myeloid leukemia cells by new ethyleneglycol-type nonphosphorus alkyl ether lipids.

A variety of ethyleneglycol-type nonphosphorus alkyl ether lipids, ether derivatives of diethyleneglycol 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 the cells differentiated into morphologically and functionally mature granulocytes. Of the compounds tested, 1-[2-[2-(octadecyloxy)ethoxy]ethoxy]-butylpyridinium mesylate (EG-6) was the most effective in inducing differentiation of HL-60 cells. Almost maximal induction of differentiation and inhibition of growth of HL-60 cells on day 6 were observed when the cells were treated with EG-6 for 1 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 ether phospholipid.