Bastian Paulina Emilia, Daca Agnieszka, Płoska Agata, Kuban-Jankowska Alicja, Kalinowski Leszek, Gorska-Ponikowska Magdalena
Department of Medical Chemistry, Medical University of Gdansk, 80-210 Gdansk, Poland.
Department of Pathology and Experimental Rheumatology, Medical University of Gdansk, 80-210 Gdansk, Poland.
Antioxidants (Basel). 2022 Oct 12;11(10):2013. doi: 10.3390/antiox11102013.
Gliomas are the most prevalent primary tumors of the central nervous system (CNS), accounting for over fifty percent of all primary intracranial neoplasms. Glioblastoma (GBM) is the most prevalent form of malignant glioma and is often incurable. The main distinguishing trait of GBM is the presence of hypoxic regions accompanied by enhanced angiogenesis. 2-Methoxyestradiol (2-ME) is a well-established antiangiogenic and antiproliferative drug. In current clinical studies, 2-ME, known as Panzem, was examined for breast, ovarian, prostate, and multiple myeloma. The SW1088 grade III glioma cell line was treated with pharmacological and physiological doses of 2-ME. The induction of apoptosis and necrosis, oxidative stress, cell cycle arrest, and mitochondrial membrane potential were established by flow cytometry. Confocal microscopy was used to detect DNA damage. The Western blot technique determined the level of nitric oxide synthase and heat shock proteins. Here, for the first time, 2-ME is shown to induce nitro-oxidative stress with the concomitant modulation of heat shock proteins (HSPs) in the SW1088 grade III glioma cell line. Crucial therapeutic strategies for GMB should address both cell proliferation and angiogenesis, and due to the above, 2-ME seems to be a perfect candidate for GBM therapy.
神经胶质瘤是中枢神经系统（CNS）中最常见的原发性肿瘤，占所有原发性颅内肿瘤的半数以上。胶质母细胞瘤（GBM）是恶性神经胶质瘤最常见的形式，通常无法治愈。GBM的主要区别特征是存在缺氧区域并伴有血管生成增强。2-甲氧基雌二醇（2-ME）是一种成熟的抗血管生成和抗增殖药物。在当前的临床研究中，对名为Panzem的2-ME进行了乳腺癌、卵巢癌、前列腺癌和多发性骨髓瘤方面的研究。用药理剂量和生理剂量的2-ME处理SW1088 III级神经胶质瘤细胞系。通过流式细胞术确定细胞凋亡和坏死、氧化应激、细胞周期停滞以及线粒体膜电位的诱导情况。共聚焦显微镜用于检测DNA损伤。蛋白质印迹技术测定一氧化氮合酶和热休克蛋白的水平。在此，首次表明2-ME在SW1088 III级神经胶质瘤细胞系中诱导硝基氧化应激并伴随热休克蛋白（HSPs）的调节。GBM的关键治疗策略应同时针对细胞增殖和血管生成，基于上述情况，2-ME似乎是GBM治疗的理想候选药物。
