Department of Physiology, University of Pretoria, P,O, Box 2034, Pretoria, 0001, South Africa.
Cancer Cell Int. 2011 Dec 12;11(1):43. doi: 10.1186/1475-2867-11-43.
In the search for anticancer agents, a promising 17-β-estradiol metabolite, 2-methoxyestradiol (2ME2) was found that exerts antiproliferative in vitro and in vivo activity. Since 2ME2 has limited biological accessibility and rapid metabolic degradation, the purpose of this study was to investigate the in vitro influence exerted by an analogue of 2ME2 namely 2-methoxyestradiol-bis-sulphamate (2MEBM) in a breast adenocarcinoma cell line (MCF-7).
This was conducted by investigating 2MEBM's in vitro influence on cell cycle progression, mitochondrial membrane potential and possible production of reactive oxygen species (ROS) generation. In vitro effects of 2MEBM on cell cycle progression was demonstrated by means of flow cytometry using propidium iodide. Hydrogen peroxide and superoxide production was investigated using 2,7-dichlorofluorescein diacetate and hydroethidine, respectively. The probable reduction in the mitochondrial membrane potential was demonstrated using a MitoCapture™ kit.
Cell cycle progression revealed the presence of a sub-G1 apoptotic peak. Reduction of mitochondrial membrane potential after exposure to 2MEBM was demonstrated and an increase in ROS production was also observed.
This study verified that 2MEBM exposure resulted in apoptosis induction, increased ROS production and reduced mitochondrial membrane potential in a tumorigenic breast epithelial cell line. Data obtained from this project contributes to the unravelling of the in vitro signal transduction of 2MEBM in tumorigenic cell lines.
在寻找抗癌药物的过程中，发现了一种有前途的 17-β-雌二醇代谢物，即 2-甲氧基雌二醇（2ME2），它具有体外和体内的抗增殖活性。由于 2ME2 的生物可及性有限且代谢迅速降解，本研究旨在研究 2ME2 的类似物 2-甲氧基雌二醇双磺酸盐（2MEBM）在乳腺腺癌细胞系（MCF-7）中产生的体外影响。
通过研究 2MEBM 对细胞周期进程、线粒体膜电位和可能产生的活性氧（ROS）生成的体外影响来进行。通过使用碘化丙啶的流式细胞术来证明 2MEBM 对细胞周期进程的体外影响。使用 2,7-二氯荧光素二乙酸酯和羟乙基噻吩分别研究了过氧化氢和超氧化物的产生。使用 MitoCaptureTM 试剂盒证明了线粒体膜电位可能降低。
细胞周期进程显示存在亚 G1 凋亡峰。暴露于 2MEBM 后，线粒体膜电位降低得到证实，并且观察到 ROS 产生增加。
本研究证实 2MEBM 暴露导致肿瘤性乳腺上皮细胞系中的细胞凋亡诱导、ROS 产生增加和线粒体膜电位降低。本项目获得的数据有助于揭示 2MEBM 在肿瘤细胞系中的体外信号转导。
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