2-Methoxyestradiol inhibits proliferation of normal and neoplastic glial cells, and induces cell death, in vitro

2-Methoxyestradiol inhibits proliferation of normal and neoplastic glial cells, and induces cell death, in vitro
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DOI:
10.1016/j.canlet.2004.04.021
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发表时间:
2004-09-15
期刊:
影响因子:
9.7
通讯作者:
Plunkett, RJ
Plunkett, RJ
中科院分区:
医学1区
文献类型:
--
作者:
Lis, A;Ciesielski, MJ;Plunkett, RJ

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2-雌二醇(E)的代谢产物甲氧基雌二醇(2 ME)抑制多种肿瘤细胞的增殖。在这项研究中,我们确定了2 ME对人胶质母细胞瘤细胞系的影响,在体外。我们比较了这些细胞与培养的星形胶质细胞从创伤成年大鼠纹状体。暴露于2 ME对人胶质母细胞瘤有很强的抗增殖作用,并引起凋亡细胞的数量增加,通过流式细胞术检测,在一些研究的细胞系。大量细胞被阻滞在细胞周期的G2/M期。同时,在所有胶质母细胞瘤细胞系中,G1期的细胞群体减少。Hoechst 33258染色显示2 ME处理的增殖细胞核形态异常。用2 ME治疗诱导了一种人胶质母细胞瘤细胞系以及增殖的成年大鼠星形胶质细胞中野生型p53的上调。我们的结论是,2 ME抑制人胶质母细胞瘤细胞系的生长,并诱导凋亡,在体外。这种化合物作为神经胶质瘤的治疗方法值得进一步研究。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
2-Methoxyestradiol (2ME), a metabolite of estradiol (E), inhibits proliferation of various tumor cells. In this study we determined the effect of 2ME on human glioblastoma cell lines, in vitro. We compared these cells with cultured astrocytes obtained from traumatized adult rat striatum. Exposure to 2ME had a strong antiproliferative effect on human glioblastoma and caused an increase in the population of apoptotic cells, detected by flow cytometry, in some of the investigated cell lines. A significant number of cells were blocked in the G2/M phase of the cell cycle. Concurrently, the population of cells in the G1 phase decreased in all glioblastoma cell lines. Staining with Hoechst 33258 revealed abnormal nuclear morphology in the proliferating cells treated with 2ME. Treatment with 2ME induced upregulation of wild type p53 in one of the human glioblastoma cell lines as well as in proliferating adult rat astrocytes. We conclude that 2ME inhibits the growth of human glioblastoma cell lines and induces apoptosis, in vitro. This compound deserves further investigation as a treatment for gliomas. (C) 2004 Elsevier Ireland Ltd. All rights reserved.