Comparison between the effect of butyric acid and its prodrug pivaloyloxymethylbutyrate on histones hyperacetylation in an HL‐60 leukemic cell line

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Abstract
A butyric acid pro‐drug, pivaloyioxymethyl butyrate, AN‐9, developed in our laboratory, was previously shown to act as a differentiation‐inducing and an anti‐cancer agent. In this study we have shown that both AN‐9 and butyric acid caused a transient hyperacetylation of histones, which returned to basal levels after 6 and 12 hr, respectively. This activity precedes the induction of differentiation elicited by both agents. AN‐9 induced acetylation of histones at a concentration one order of magnitude lower than butyric acid. Pre‐treatment of the cells with esterase(s) inhibitors diminished the ability of AN‐9 to inhibit proliferation and induce differentiation. The above suggests that the intracellular release of butyric acid fragment, from the pro‐drug, is catalyzed by cellular esterase(s).
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