Euphol arrests breast cancer cells at the G1 phase through the modulation of cyclin D1, p21 and p27 expression
Euphol arrests breast cancer cells at the G1 phase through the modulation of cyclin D1, p21 and p27 expression
复制标题
Euhol 通过调节细胞周期蛋白 D1、p21 和 p27 的表达将乳腺癌细胞阻滞在 G1 期。
DOI：
10.3892/mmr.2013.1650
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发表时间：
2013-10-01
影响因子：
3.4
通讯作者：
Kang, Jiuhong
中科院分区：
文献类型：
--
作者：
Wang, Lin;Wang, Guiying;Kang, Jiuhong
Euphorbia tirucalli是一种长期用于治疗各种癌症的药物。然而，其抗癌作用的机制尚未阐明。在本研究中，我们研究了Euphol，一个四环三萜醇从Euphorbia tirucalli的汁液中分离出来，在T47 D人乳腺癌细胞的抗癌作用。用不同剂量的Euphol处理细胞24、48和72 h后，分别分析细胞增殖、细胞周期以及细胞周期调控分子的mRNA和蛋白水平。用大戟酚处理细胞导致细胞活力降低，这伴随着G1期细胞的积累。进一步的研究表明，大戟处理下调细胞周期蛋白D1的表达和Rb的低磷酸化。此外，这种效应与细胞周期蛋白依赖性激酶2（CDK 2）表达的下调和CDK抑制剂p21和p27的上调相关。还观察到细胞周期蛋白A和B1的表达水平降低，分别对应于S期和G2/M期细胞分布的减少。这些结果表明，大戟酚是一种活性剂，在大戟tirucalli发挥抗癌活性，通过阻止癌细胞的细胞周期。
Euphorbia tirucalli is a long-established treatment for a wide variety of cancers. However, the mechanism of its anticancer effect is yet to be elucidated. In the present study, we examined the anticancer effect of euphol, a tetracyclic triterpene alcohol isolated from the sap of Euphorbia tirucalli, in T47D human breast cancer cells. Following the treatment of cells with different doses of euphol for 24, 48 and 72 h, the cell proliferation, cell cycle, and mRNA and protein levels of cell cycle regulatory molecules were analyzed, respectively. Treatment of the cells with euphol resulted in decreased cell viability, which was accompanied by an accumulation of cells in the G1 phase. Further studies demonstrated that euphol treatment downregulated cyclin D1 expression and the hypophosphorylation of Rb. Furthermore, this effect was correlated with the downregulation of cyclin-dependent kinase 2 (CDK2) expression and the upregulation of the CDK inhibitors p21 and p27. Reduced expression levels of cyclin A and B1 were also observed, corresponding to the decreased distribution of cells in the S and G2/M phases, respectively. These findings indicated that euphol is an active agent in Euphorbia tirucalli that exerts anticancer activity by arresting the cell cycle of cancer cells.