Justus Liebig University, Giessen, Germany.
Eur Rev Med Pharmacol Sci. 2013 Mar;17(5):668-72.
Atherosclerosis and stent re-stenosis are problems that are accompanied with high morbidity and mortality. Endothelial cell proliferation plays a role in both diseases, so the quest for potent inhibitors is still ongoing.
The flavonoid pinostrobin previously showed cytotoxic effects on different cell lines. In this investigation, we tested the antiproliferative effect of pinostrobin on human umbilical vein endothelial cells (HUVEC).
The effect of pinostrobin on human umbilical vein endothelial cells after 1 hour and after 48 hours of treatment was tested. A dose- and time-dependent antiproliferative effect of pinostrobin was observed.
After 1 hour of treatment, no significant differences between the control group and the cells treated with pinostrobin could be detected. After 48 h of pinostrobin treatment, the number of cells decreased significantly. Higher doses had stronger inhibitory effects on the proliferation. Furthermore, we tested the change of membrane potential on cells that were treated with different concentrations of pinostrobin. We could show that the change of membrane potential was also time- as well as dose-dependent.
Our hypothesis is that pinostrobin leads to depolarisation of the cell potential of endothelial cells. Since the membrane potential remains less negative, this could lead to instability of the membrane, resulting in cell death.
动脉粥样硬化和支架再狭窄是发病率和死亡率都很高的问题。内皮细胞增殖在这两种疾病中都起作用,因此对有效抑制剂的探索仍在继续。
先前黄酮类化合物 pinostrobin 对不同细胞系显示出细胞毒性作用。在这项研究中,我们测试了 pinostrobin 对人脐静脉内皮细胞(HUVEC)的抗增殖作用。
测试了 pinostrobin 对人脐静脉内皮细胞 1 小时和 48 小时后的作用。观察到 pinostrobin 具有剂量和时间依赖性的抗增殖作用。
治疗 1 小时后,对照组和用 pinostrobin 处理的细胞之间没有明显差异。经过 48 小时的 pinostrobin 处理后,细胞数量明显减少。较高的剂量对增殖的抑制作用更强。此外,我们测试了用不同浓度的 pinostrobin 处理的细胞的膜电位变化。我们可以证明膜电位的变化也是时间和剂量依赖性的。
我们的假设是,pinostrobin 导致内皮细胞的细胞电位去极化。由于膜电位保持得不够负,这可能导致膜不稳定,导致细胞死亡。