Myricetin induces G2/M phase arrest in HepG2 cells by inhibiting the activity of the cyclin B/Cdc2 complex.
Myricetin induces G2/M phase arrest in HepG2 cells by inhibiting the activity of the cyclin B/Cdc2 complex.
复制标题
DOI：
10.3892/mmr.2011.417
复制
发表时间：
2011-03
影响因子：
3.4
通讯作者：
Xiao-Hong Zhang;Zuquan Zou;Chen-Wei Xu;Yingzhuo Shen;Duo Li
中科院分区：
文献类型：
--
作者：
Xiao-Hong Zhang;Zuquan Zou;Chen-Wei Xu;Yingzhuo Shen;Duo Li
杨梅素是一种天然存在的黄酮醇，已被证明可抑制人肝癌细胞株HepG2的增殖，并诱导G2/M期停滞。然而，杨梅素活性的潜在机制尚未被揭示。本研究旨在阐明杨梅素诱导HepG2细胞周期停滞的分子机制。四甲基偶氮唑盐比色法证实杨梅素作用于HepG2细胞后，细胞周期发生G2/M期阻滞。Western印迹分析显示，杨梅素可上调细胞内P53/p21级联蛋白水平，显著降低细胞周期蛋白B1和CDc2蛋白水平。此外，杨梅素处理导致Thr14/Tyr15磷酸化(非活性)CDc2和p27上调，CDK7蛋白下调，以及CDK7介导的Thr161磷酸化(活性)CDc2。这些结果表明，杨梅素诱导的细胞周期蛋白B/CDc2复合体活性降低，导致细胞周期阻滞于G2/M期。这一新的发现为杨梅素在肝细胞癌治疗中的潜在应用提供了洞察力。
Myricetin, a naturally occurring flavonol, has been shown to inhibit the proliferation of human hepatoma HepG2 cells and to induce G2/M phase arrest. However, the underlying mechanisms of Myricetin activity have yet to be revealed. The aim of the present study was to clarify the molecular mechanisms of cell cycle arrest induced by myricetin in HepG2 cells. The MTT assay confirmed that exposure of HepG2 cells to myricetin triggered G2/M phase arrest. Western blot analysis showed that myricetin increased the protein levels of the p53/p21 cascade, and markedly decreased Cdc2 and cyclin B1 protein levels in HepG2 cells. Additionally, myricetin treatment resulted in the up-regulation of Thr14/Tyr15 phosphorylated (inactive) Cdc2 and p27, and the down-regulation of CDK7 kinase protein, as well as CDK7-mediated Thr161 phosphorylated (active) Cdc2. These data indicate that a decrease in cyclin B/Cdc2 complex activity mediated G2/M phase arrest induced by myricetin in HepG2 cells. This novel finding provides insight into the potential applications of myricetin in the treatment of hepatocellular carcinoma.