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多酚类分子和组蛋白去乙酰化酶抑制剂对结肠癌细胞生长的抑制和分化标志物的诱导。

Inhibition of growth and induction of differentiation markers by polyphenolic molecules and histone deacetylase inhibitors in colon cancer cells.

机构信息

Department of Biochemistry and Molecular Biology, UMDNJ - New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.

出版信息

Anticancer Res. 2010 Feb;30(2):311-8.

PMID:20332434
Abstract

Previously we found that a fruit-derived polyphenol fraction caused an inhibition of proliferation and an induction of differentiation markers in Caco-2 human colon cancer cells. In the present work, we sought to determine if individual polyphenols would exert similar actions. Proliferation was inhibited by several polyphenolic molecules including gallic acid, ellagic acid, quercetin and resveratrol. In Caco-2 cells, growth inhibition was accompanied by increased specific activities of two differentiation markers, alkaline phosphatase and dipeptidyl peptidase, but not of aminopeptidase. Increased enzyme activities were not seen in HT29 and SW1116 colon cancer cells. In Caco-2 cells there were additive effects of butyrate or valproate and polyphenolic molecules. Histone acetylation was not greatly affected by the polyphenols. Cycloheximide inhibited protein synthesis in the 3 cell types examined but paradoxically, in Caco-2 cells it caused increased specific activities of alkaline phosphatase and dipeptidyl peptidase. Several plant polyphenols can inhibit the growth of colon cancer cells but increased specific activity of some differentiation markers seen in Caco-2 cells did not appear to be a general phenomenon in colon cancer cells.

摘要

先前我们发现,一种水果来源的多酚混合物能抑制 Caco-2 人结肠癌细胞的增殖并诱导其分化标志物的产生。在本研究中,我们试图确定是否单独的多酚也具有相似的作用。包括没食子酸、鞣花酸、槲皮素和白藜芦醇在内的几种多酚类分子都能抑制增殖。在 Caco-2 细胞中,生长抑制伴随着两种分化标志物,碱性磷酸酶和二肽基肽酶的比活性增加,但氨基肽酶的比活性没有增加。在 HT29 和 SW1116 结肠癌细胞中未观察到酶活性的增加。在 Caco-2 细胞中,丁酸盐或丙戊酸盐与多酚类分子具有相加作用。组蛋白乙酰化受多酚影响不大。细胞周期蛋白 D1 在这 3 种被检测的细胞类型中都能抑制蛋白合成,但矛盾的是,在 Caco-2 细胞中,它引起碱性磷酸酶和二肽基肽酶的比活性增加。一些植物多酚可以抑制结肠癌细胞的生长,但在 Caco-2 细胞中观察到的一些分化标志物的比活性增加似乎不是结肠癌细胞的普遍现象。

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