Discordant effects of butyrate analogues on erythroleukemia cell proliferation, differentiation and histone deacetylase.

Actions of butyrate and structural analogues on histone deacetylase activity were compared with effects on proliferation and differentiation of erythroleukemia cells. Proliferation was inhibited by 5 mM tert- butylacetate, phenylacetate, phenylbutyrate, 3-bromopropionate and ethyl butyrate without induction of hemoglobin synthesis. n - Butyramide was a stronger inhibitor of cell proliferation and a more effective inducer of hemoglobin synthesis than isobutyramide. The data from combination studies were compatible with butyramide and isobutyramide being weaker agonists that competed for a common site with butyrate. Butyramide and isobutyramide were weaker inhibitors of histone deacetylase than 4-phenylbutyrate and phenylacetate, which in turn were less effective than 3-bromopropionate and butyrate. Butyrate and analogues had similar inhibitory effects on histone deacetylase activity in nuclei from mouse DS19 cells and human K562 cells. Effects on histone deacetylase did not show a consistent correlation with inhibition of cell proliferation or induction of hemoglobin synthesis.