Induction of histone acetylation and growth regulation in eryrthroleukemiacells by 4-phenylbutyrate and structural analogs

The objective of this investigation was to study the relationship between h istone acetylation and growth inhibition by 4-phenylbutyrate and structural analogs. Inhibition of growth gf DS19 mouse erythroleukemia cells and K562 human leukemic cells by 4-phenylbutyrate did not appear to be mediated by glutamine depletion. Vanadate blocked differentiation of DS19 cells bur did not affect the hyperacetylation of histones. 2-phenylbutyrate was a more e ffective inhibitor of cell proliferation than 3-phenylbutyrate but was less effective as an inducer of histone acetylation. 4-Phenylbutyrate was a mol e effective inhibitor of histone deacetylase and inducer of histone acetyla tion than the structural analogs examined including 2- and 3-phenylbutyrate , cinnamate, methoxycinnamate, 2-phenoxybutyrate and phenoxyacetate.