Wei Juan, Su Hailan, Bi Yang, Li Jixin, Feng Lidan, Sheng Wenjun
College of Food Science and Engineering, Gansu Agricultural University, Lanzhou, Gansu 730070, P.R. China.
Exp Ther Med. 2018 Apr;15(4):3917-3923. doi: 10.3892/etm.2018.5892. Epub 2018 Feb 26.
As a major cancer type in females, cervical cancer has been explored in depth by researchers. HeLa is a cervical cancer cell line. Isorhamnetin is an O-methylated flavonol that is primarily extracted from sea buckthorn. In the present study, the anti-proliferative effect of isorhamnetin on HeLa cells was evaluated using a Trypan blue dye exclusion assay. Isorhamnetin inhibited the cell proliferation in a time- and dose-dependent manner. Flow cytometric analysis of the cell cycle distribution revealed that isorhamnetin inhibited the cell cycle progression of HeLa by causing G2/M phase arrest and decreasing the proportion of cells in G1 phase. In addition, western blot analysis was performed to evaluate the presence of certain cell cycle-associated proteins. It was demonstrated that isorhamnetin inhibited the protein expression of cyclin B1, cell division cycle 25C (Cdc25C) and Cdc2, but enhanced checkpoint kinase 2 (Chk2), Cdc25C and Cdc2 phosphorylation. In addition, tubulin depolymerization participated in the isorhamnetin-induced cell cycle arrest in G2/M phase. In conclusion, the present results indicated that the anti-proliferative action of isorhamnetin is associated with arrest of the cell cycle in G2/M phase, which is a consequence of activation of the ataxia telangiectasia mutated Chk2 pathway and disruption of microtubule function.
作为女性主要的癌症类型，宫颈癌已被研究人员深入探索。HeLa是一种宫颈癌细胞系。异鼠李素是一种主要从沙棘中提取的O-甲基化黄酮醇。在本研究中，使用台盼蓝染料排除试验评估了异鼠李素对HeLa细胞的抗增殖作用。异鼠李素以时间和剂量依赖性方式抑制细胞增殖。细胞周期分布的流式细胞术分析表明，异鼠李素通过导致G2/M期阻滞并降低G1期细胞比例来抑制HeLa细胞的细胞周期进程。此外，进行了蛋白质印迹分析以评估某些细胞周期相关蛋白的存在情况。结果表明，异鼠李素抑制细胞周期蛋白B1、细胞分裂周期25C（Cdc25C）和Cdc2的蛋白表达，但增强了关卡激酶2（Chk2）、Cdc25C和Cdc2的磷酸化。此外，微管解聚参与了异鼠李素诱导的G2/M期细胞周期阻滞。总之，目前的结果表明，异鼠李素的抗增殖作用与G2/M期细胞周期阻滞有关，这是共济失调毛细血管扩张症突变的Chk2途径激活和微管功能破坏的结果。
