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Comparison between the effect of butyric acid and its prodrug pivaloyloxymethylbutyrate on histones hyperacetylation in an HL‐60 leukemic cell line
Author(s) -
Aviram Adina,
Zimrah Yael,
Shaklai Mali,
Nudelman Abraham,
Rephaeli Ada
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910560625
Subject(s) - butyric acid , butyrate , acetylation , histone , prodrug , intracellular , cellular differentiation , chemistry , cell culture , biochemistry , cytosol , microbiology and biotechnology , enzyme , biology , dna , genetics , fermentation , gene
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).