Gallic acid inhibits ribonucleotide reductase and cyclooxygenases in human HL-60 promyelocytic leukemia cells
Gallic acid inhibits ribonucleotide reductase and cyclooxygenases in human HL-60 promyelocytic leukemia cells
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DOI：
10.1016/j.canlet.2006.01.001
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发表时间：
2007-01-08
期刊：
影响因子：
9.7
通讯作者：
Szekeres, Thomas
中科院分区：
文献类型：
--
作者：
Madlener, Sibylle;Illmer, Christoph;Szekeres, Thomas
没食子酸（GA）是一种天然存在的多羟基酚类化合物，是一种优良的自由基清除剂。在这项研究中，我们研究了它对人早幼粒白血病细胞系HL-60的细胞毒性和生化作用。GA引起的脱氧核苷三磷酸（dNTP）池大小的显着不平衡，表明核糖核苷酸还原酶抑制。此外，GA诱导HL-60细胞中的剂量依赖性凋亡（80 μ M GA导致39%的细胞中的凋亡诱导），并减弱细胞周期从G 0/G1期到S期的进展（60 μ M GA使G 0/G1期的细胞数量加倍，与未处理的对照相比，从22%到44%）。我们进一步测定了抑制环加氧酶I和II的IC 50值分别为3.5和4.4 nM。当GA和另一种RR抑制剂曲米多克斯同时处理细胞时，可以观察到高度协同的生长抑制作用。总之，我们确定了GA的新的生化作用，这可能是进一步的临床前和体内研究的基础。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Gallic acid (GA) is a naturally occurring polyhydroxyphenolic compound and an excellent free radical scavenger. In this study, we examined its cytotoxic and biochemical effects on the human HL-60 promyelocytic leukemia cell line. GA caused a significant imbalance of deoxynucleosidetriphosphate (dNTP) pool sizes, indicating ribonucleotide reductase inhibition. Moreover, GA induced dose-dependent apoptosis in HL-60 cells (80 mu M GA led to the induction of apoptosis in 39% of cells) and attenuated progression from G0/G1 to the S phase of the cell cycle (60 tM GA doubled the number of cells in G0/G1 phase from 22 to 44% when compared to untreated controls). We further determined IC50 values of 3.5 and 4.4 nM for the inhibition of cyclooxygenases I and II, respectively. When cells were simultaneously treated with GA and trimidox, another inhibitor of RR, highly synergistic growth inhibitory effects could be observed. Taken together, we identified novel biochemical effects of GA which could be the basis for further preclinical and in vivo studies. (c) 2006 Elsevier Ireland Ltd. All rights reserved.