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.
Lea
M A
MA
Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, Newark 07103, USA. lea@umdnj.edu
Randolph
V M
VM
Hodge
S K
SK
D000081:Acetamides / Q000494:pharmacology; D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006131:Growth Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D010654:Phenylbutyrates / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D014638:Vanadates / Q000494:pharmacology
D000081:Acetamides; D000970:Antineoplastic Agents; D002087:Butyrates; D002934:Cinnamates; D006131:Growth Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009363:Neoplasm Proteins; D010654:Phenylbutyrates; D014638:Vanadates; C036032:3-phenylbutyric acid; C063318:4-methoxycinnamic acid; C075773:4-phenylbutyric acid; D006655:Histone Deacetylases; C014026:hexamethylene bisacetamide; C039714:2-phenylbutyric acid