Chen Jie, Kang Jiu-Hong
School of Life Sciences, Lanzhou University, Lanzhou, China.
Pharmazie. 2005 Nov;60(11):856-60.
Quercetin (QU) and trichostatin A (TSA) are promising anticancer drugs. While QU mainly exerts its anticancer activity through scavenging reactive oxygen species (ROS), the anticancer activity of TSA was attributed to its inhibition on histone deacetylases (HDAC). In the present study it was investigated, whether the combination of QU and TSA could improve their anticancer activity against human leukemia cells (HL-60). The cytotoxicity of QU and TSA increased in a time and dose-dependent manner. QU (10, 20 and 40 microM) was able to diminish the ROS generation (indicated by the level of malondialdehyde, MDA) but showed no influence on the histone acetylation in HL-60 cells; on the contrary, TSA (20, 40, 80 and 160 nM) showed no inhibition on ROS generation but significantly increased the histone acetylation, indicating the possible role of both scavenging ROS and increasing histone acetylation in the induction of cell death in HL-60 cells. This conclusion was confirmed by the findings that the combinations of QU and TSA at different concentrations could not only diminish ROS generation, but also increase histone acetylation, and hence showed more significant cytotoxicity in HL-60 cells than either of its components. Collectively, the present data indicate that a combination of QU and TSA can cooperatively kill HL-60 cells through the combination of their activities of scavenging ROS and increasing histone acetylation.
槲皮素（QU）和曲古抑菌素A（TSA）都是很有前景的抗癌药物。QU主要通过清除活性氧（ROS）发挥其抗癌活性，而TSA的抗癌活性则归因于其对组蛋白脱乙酰酶（HDAC）的抑制作用。在本研究中，探讨了QU和TSA联合使用是否能提高它们对人白血病细胞（HL-60）的抗癌活性。QU和TSA的细胞毒性呈时间和剂量依赖性增加。QU（10、20和40微摩尔）能够减少ROS的产生（以丙二醛，即MDA的水平表示），但对HL-60细胞中的组蛋白乙酰化没有影响；相反，TSA（20、40、80和160纳摩尔）对ROS的产生没有抑制作用，但显著增加了组蛋白乙酰化，表明清除ROS和增加组蛋白乙酰化在诱导HL-60细胞死亡中可能都发挥了作用。不同浓度的QU和TSA联合使用不仅能减少ROS的产生，还能增加组蛋白乙酰化，因此在HL-60细胞中显示出比其任何一种成分都更显著的细胞毒性，这一发现证实了上述结论。总的来说，目前的数据表明，QU和TSA联合使用可以通过其清除ROS和增加组蛋白乙酰化的活性协同杀死HL-60细胞。
