神经元型一氧化氮合酶的核劫持诱导的DNA链断裂作为2-甲氧基雌二醇的抗癌作用。
DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol.
作者信息
Gorska Magdalena, Kuban-Jankowska Alicja, Zmijewski Michal, Marino Gammazza Antonella, Cappello Francesco, Wnuk Maciej, Gorzynik Monika, Rzeszutek Iwona, Daca Agnieszka, Lewinska Anna, Wozniak Michal
机构信息
Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
Department of Histology, Medical University of Gdansk, Gdansk, Poland.
出版信息
Oncotarget. 2015 Jun 20;6(17):15449-63. doi: 10.18632/oncotarget.3913.
2-Methoxyestradiol (2-ME) is a physiological metabolite of 17β-estradiol. At pharmacological concentrations, 2-ME inhibits colon, breast and lung cancer in tumor models. Here we investigated the effect of physiologically relevant concentrations of 2-ME in osteosarcoma cell model. We demonstrated that 2-ME increased nuclear localization of neuronal nitric oxide synthase, resulting in nitro-oxidative DNA damage. This in turn caused cell cycle arrest and apoptosis in osteosarcoma cells. We suggest that 2-ME is a naturally occurring hormone with potential anti-cancer properties.
2-甲氧基雌二醇（2-ME）是17β-雌二醇的一种生理代谢产物。在药理浓度下，2-ME在肿瘤模型中可抑制结肠癌、乳腺癌和肺癌。在此，我们研究了生理相关浓度的2-ME在骨肉瘤细胞模型中的作用。我们证明，2-ME增加了神经元型一氧化氮合酶的核定位，导致硝基氧化DNA损伤。这进而导致骨肉瘤细胞的细胞周期停滞和凋亡。我们认为，2-ME是一种具有潜在抗癌特性的天然激素。
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