Lea M A, Tulsyan N
Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, Newark 07103, USA.
Anticancer Res. 1995 May-Jun;15(3):879-83.
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.
将丁酸及其结构类似物对组蛋白脱乙酰酶活性的作用与对红白血病细胞增殖和分化的影响进行了比较。5 mM的叔丁基乙酸酯、苯乙酸酯、苯丁酸酯、3-溴丙酸酯和丁酸乙酯可抑制细胞增殖，但不诱导血红蛋白合成。正丁酰胺比异丁酰胺是更强的细胞增殖抑制剂和更有效的血红蛋白合成诱导剂。联合研究的数据表明，丁酰胺和异丁酰胺是较弱的激动剂，它们与丁酸竞争共同位点。丁酰胺和异丁酰胺对组蛋白脱乙酰酶的抑制作用比4-苯丁酸酯和苯乙酸酯弱，而4-苯丁酸酯和苯乙酸酯又比3-溴丙酸酯和丁酸的效果差。丁酸及其类似物对小鼠DS19细胞和人K562细胞核中的组蛋白脱乙酰酶活性具有相似的抑制作用。对组蛋白脱乙酰酶的影响与细胞增殖抑制或血红蛋白合成诱导之间没有一致的相关性。
