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

Anticancer Res. May-Jun 1999;19(3A):1971-6.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / pharmacology
  • Acetylation / drug effects
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Butyrates / pharmacology
  • Cell Division / drug effects
  • Cinnamates / pharmacology
  • Drug Screening Assays, Antitumor
  • Growth Inhibitors / pharmacology*
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / metabolism
  • Histones / metabolism*
  • Humans
  • Leukemia, Erythroblastic, Acute / metabolism
  • Leukemia, Erythroblastic, Acute / pathology*
  • Mice
  • Neoplasm Proteins / metabolism*
  • Phenylbutyrates / pharmacology*
  • Protein Processing, Post-Translational / drug effects*
  • Vanadates / pharmacology


  • Acetamides
  • Antineoplastic Agents
  • Butyrates
  • Cinnamates
  • Growth Inhibitors
  • Histone Deacetylase Inhibitors
  • Histones
  • Neoplasm Proteins
  • Phenylbutyrates
  • Vanadates
  • 3-phenylbutyric acid
  • 4-methoxycinnamic acid
  • 4-phenylbutyric acid
  • Histone Deacetylases
  • hexamethylene bisacetamide
  • 2-phenylbutyric acid