Madlener Sibylle, Illmer Christoph, Horvath Zsuzsanna, Saiko Philipp, Losert Annemarie, Herbacek Irene, Grusch Michael, Elford Howard L, Krupitza Georg, Bernhaus Astrid, Fritzer-Szekeres Monika, Szekeres Thomas
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, General Hospital of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Cancer Lett. 2007 Jan 8;245(1-2):156-62. doi: 10.1016/j.canlet.2006.01.001. Epub 2006 Feb 20.
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 (80microM 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 (60microM GA doubled the number of cells in G0/G1 phase from 22 to 44% when compared to untreated controls). We further determined IC(50) values of 3.5 and 4.4nM 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.
没食子酸（GA）是一种天然存在的多羟基酚类化合物，也是一种出色的自由基清除剂。在本研究中，我们检测了其对人HL-60早幼粒细胞白血病细胞系的细胞毒性和生化作用。GA导致脱氧核苷三磷酸（dNTP）池大小显著失衡，表明核糖核苷酸还原酶受到抑制。此外，GA诱导HL-60细胞发生剂量依赖性凋亡（80μM GA导致39%的细胞发生凋亡），并减弱细胞周期从G0/G1期到S期的进程（与未处理的对照相比，60μM GA使G0/G1期的细胞数量从22%翻倍至44%）。我们进一步确定GA对环氧合酶I和II抑制作用的半数抑制浓度（IC50）值分别为3.5和4.4nM。当细胞同时用GA和另一种核糖核苷酸还原酶抑制剂曲美沙星处理时，可观察到高度协同的生长抑制作用。综上所述，我们确定了GA的新生化作用，这可能是进一步进行临床前和体内研究的基础。
