Neuronal nitric oxide synthase induction in the antitumorigenic and neurotoxic effects of 2-methoxyestradiol.
Neuronal nitric oxide synthase induction in the antitumorigenic and neurotoxic effects of 2-methoxyestradiol.
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DOI：
10.3390/molecules190913267
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发表时间：
2014-08-28
期刊：
影响因子：
--
通讯作者：
Wozniak M
中科院分区：
文献类型：
--
作者：
Gorska M;Kuban-Jankowska A;Zmijewski MA;Gorzynik M;Szkatula M;Wozniak M
目的：2-甲氧基雌二醇是一种天然17β-雌二醇衍生物，是一种新型的、有效的抗癌药物，目前正在进行高级临床试验。本研究的主要目的是研究2-甲氧基雌二醇对骨肉瘤细胞的抗癌活性及其可能的神经退行性作用。我们使用了一个实验模型的神经毒性和抗癌活性的生理剂，2-甲氧基乙烯。因此，我们使用高转移性骨肉瘤143 B和小鼠永生化海马HT 22细胞系。用药理学浓度（1 μM、10 μM）的2-甲氧基乙烯醇处理细胞。实验：采用蛋白质印迹法测定神经元型一氧化氮合酶和3-硝基酪氨酸蛋白水平。MTT法检测细胞活力，PI/Annexin V染色检测细胞凋亡，DNA片段化ELISA检测细胞凋亡。用流式细胞术测定细胞内一氧化氮水平。结果：在这里，我们证明了神经退行性疾病和癌症的信号通路可能重叠。我们提供的证据表明，与17β-雌二醇相反，2-甲氧基雌二醇特异性影响神经元型一氧化氮合酶，并增加3-硝基酪氨酸水平，导致骨肉瘤和永生化海马细胞死亡。结论：我们报告了2-甲氧基乙烯的双重方面，它导致癌细胞死亡，但另一方面可能作为神经毒素发挥关键作用。
Objective: 2-Methoxyestradiol, one of the natural 17β-estradiol derivatives, is a novel, potent anticancer agent currently being evaluated in advanced phases of clinical trials. The main goal of the study was to investigate the anticancer activity of 2-methoxy-estradiol towards osteosarcoma cells and its possible neurodegenerative effects. We used an experimental model of neurotoxicity and anticancer activity of the physiological agent, 2-methoxyestradiol. Thus, we used highly metastatic osteosarcoma 143B and mouse immortalized hippocampal HT22 cell lines. The cells were treated with pharmacological (1 μM, 10 μM) concentrations of 2-methoxyestradiol. Experimental: Neuronal nitric oxide synthase and 3-nitrotyrosine protein levels were determined by western blotting. Cell viability and induction of cell death were measured by MTT and PI/Annexin V staining and a DNA fragmentation ELISA kit, respectively. Intracellular levels of nitric oxide were determined by flow cytometry. Results: Here we demonstrated that the signaling pathways of neurodegenerative diseases and cancer may overlap. We presented evidence that 2-methoxyestradiol, in contrast to 17β-estradiol, specifically affects neuronal nitric oxide synthase and augments 3-nitrotyrosine level leading to osteosarcoma and immortalized hippocampal cell death. Conclusions: We report the dual facets of 2-methoxyestradiol, that causes cancer cell death, but on the other hand may play a key role as a neurotoxin.
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影响因子：
3
作者：
Kulke, Matthew H.;Chan, Jennifer A.;Meyerhardt, Jeffrey A.;Zhu, Andrew X.;Abrams, Thomas A.;Blaszkowsky, Lawrence S.;Regan, Eileen;Sidor, Carolyn;Fuchs, Charles S.
通讯作者：
Fuchs, Charles S.
影响因子：
4.7
作者：
Heigold, S;Sers, C;Bauer, G
通讯作者：
Bauer, G
影响因子：
4.1
作者：
Maran, A;Zhang, M;Turner, RT
通讯作者：
Turner, RT
影响因子：
3.6
作者：
Dahut, WL;Lakhani, NJ;Figg, WD
通讯作者：
Figg, WD
影响因子：
3.2
作者：
Chi, SN;Conklin, LS;Gorlick, R
通讯作者：
Gorlick, R