Induction of histone acetylation and inhibition of growth of mouse erythroleukemia cells by S-allylmercaptocysteine
Induction of histone acetylation and inhibition of growth of mouse erythroleukemia cells by S-allylmercaptocysteine
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DOI：
10.1207/s15327914nc431_11
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发表时间：
2002-01-01
影响因子：
2.9
通讯作者：
desBordes, C
中科院分区：
文献类型：
--
作者：
Lea, MA;Rasheed, M;desBordes, C
大蒜素和s -烯丙基巯基半胱氨酸在微摩尔浓度范围内，丁酸烯丙基、烯丙基苯砜和s -烯丙基半胱氨酸在毫摩尔浓度范围内对DS19小鼠红白血病细胞有生长抑制作用。用与抑制细胞增殖的浓度相似的烯丙基化合物孵育细胞，可诱导组蛋白乙酰化增加。在Caco-2型人结肠癌细胞和T47D型人乳腺癌细胞中也观察到s -烯丙基巯基半胱氨酸诱导组蛋白乙酰化。与对组蛋白乙酰化的影响相反，当DS19细胞与25 am s -烯丙基巯基半胱氨酸孵育时，磷酸盐掺入组蛋白的减少。丁酸烯丙基抑制组蛋白去乙酰化酶活性，但烯丙基硫化合物对组蛋白去乙酰化酶活性几乎没有影响。与s -烯丙基巯基半胱氨酸或异硫氰酸烯丙基孵育DS19细胞时，组蛋白去乙酰化酶和组蛋白乙酰转移酶的下调程度相似。s -烯丙基巯基半胱氨酸对组蛋白乙酰化的诱导不被蛋白酶体抑制剂阻断。s -烯丙基巯基半胱氨酸诱导组蛋白乙酰化的机制仍有待研究。这可能部分与代谢烯丙基硫醇有关，烯丙基硫醇是一种更有效的组蛋白去乙酰化酶抑制剂。
Growth-inhibitory effects on DS19 mouse erythroleukemia cells were seen in the micromolar concentration range with allicin and S-allylmercaptocysteine and in the millimolar range with allyl butyrate, allyl phenyl sulfone, and S-allyl cysteine. Increased acetylation of histones was induced by incubation of cells with the allyl compounds at concentrations similar to those that resulted in the inhibition of cell proliferation. The induction of histone acetylation by S-allylmercaptocysteine was also observed in Caco-2 human colon cancer cells and T47D human breast cancer cells. In contrast to the effect on histone acetylation, there was a decrease in the incorporation of phosphate into histones when DS19 cells were incubated with 25 am S-allylmereaptocysteine. Histone deacetylase activity was inhibited by allyl butyrate, but there was little or no effect with the allyl sulfur compounds examined in this study. A similar degree of downregulation of histone deacetylase and histone acetyltransferase was observed when DS19 cells were incubated with S-allylmercaptocysteine or allyl isothiocyanate. The induction of histone acetylation by S-allylmercaptocysteine was not blocked by a proteasome inhibitor. The mechanism by which S-allylmercaptocysteine induces histone acetylation remains to be characterized. It may be related in part to metabolism to allyl mercaptan, which is a more effective inhibitor of histone deacetylase.