Inhibition of phosphatidylcholine biosynthesis following induction of apoptosis in HL-60 cells

Induction of apoptosis in HL-60 cells, using a variety of cytotoxic drugs, resulted, in all cases, in inhibition of CDP-choline:1,2-diacylglycerol cho line phosphotransferase, leading to an accumulation of its substrate, CDP-c holine, and inhibition of phosphatidylcholine biosynthesis. Incubation of t he cells with phosphatidylcholine reduced the number displaying an apoptoti c morphology following drug treatment, and this was inversely related to th e degree to which the drugs inhibited phosphatidylcholine biosynthesis. Inh ibition of choline phosphotransferase by two of the drugs, farnesol and che lerythrine, was shown to be due to direct inhibition of the enzyme, while i nhibition by the other drugs, etoposide and camptothecin, could be explaine d by the intracellular acidification that followed induction of apoptosis.