Induction of histone acetylation and growth regulation in eryrthroleukemia cells by 4-phenylbutyrate and structural analogs.

The objective of this investigation was to study the relationship between histone acetylation and growth inhibition by 4-phenylbutyrate and structural analogs. Inhibition of growth of 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 but did not affect the hyperacetylation of histones. 2-phenylbutyrate was a more effective inhibitor of cell proliferation than 3-phenylbutyrate but was less effective as an inducer of histone acetylation. 4-Phenylbutyrate was a more effective inhibitor of histone deacetylase and inducer of histone acetylation than the structural analogs examined including 2- and 3-phenylbutyrate, cinnamate, methoxycinnamate, 2-phenoxybutyrate and phenoxyacetate.