Gorska Magdalena, Kuban-Jankowska Alicja, Milczarek Ryszard, Wozniak Michal
Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland
Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
Anticancer Res. 2016 Apr;36(4):1693-8.
Neuroblastoma is one of the most common childhood malignancies and the primary cause of death from pediatric cancer. Derivatives of 17β-estradiol, 2-methoxyestradiol, as well as selective estrogen receptor modulators, such as fulvestrant, are novel potentially active anticancer agents. In particular, 2-methoxyestradiol is effective in treatment of numerous malignancies, including breast and prostate cancer, Ewing sarcoma, and osteosarcoma. Herein, we treated neuroblastoma SH-SY5Y cells with physiologically and pharmacologically relevant concentrations of 2-methoxyestradiol. We used flow cytometry in order to determine cell viability, cell death, level of nitric oxide and mitochondrial membrane potential. We demonstrated that at pharmacologically relevant concentrations, 2-methoxyestradiol results in induction of apoptosis of neuroblastoma SH-SY5Y cells via nitric oxide generation and reduction of mitochondrial membrane potential. Based on the obtained data, we propose that 2-methoxyestradiol may be a natural modulator of cancer cell death and survival through nitro-oxidative stress-dependent mechanisms. Moreover, the results confirm the efficiency of 2-methoxyestradiol in treatment of neuroblastoma.
神经母细胞瘤是儿童期最常见的恶性肿瘤之一，也是儿童癌症死亡的主要原因。17β-雌二醇的衍生物2-甲氧基雌二醇以及选择性雌激素受体调节剂，如氟维司群，都是新型的潜在活性抗癌药物。特别是，2-甲氧基雌二醇对包括乳腺癌、前列腺癌、尤因肉瘤和骨肉瘤在内的多种恶性肿瘤有效。在此，我们用生理和药理相关浓度的2-甲氧基雌二醇处理神经母细胞瘤SH-SY5Y细胞。我们使用流式细胞术来确定细胞活力、细胞死亡、一氧化氮水平和线粒体膜电位。我们证明，在药理相关浓度下，2-甲氧基雌二醇通过一氧化氮生成和线粒体膜电位降低诱导神经母细胞瘤SH-SY5Y细胞凋亡。基于获得的数据，我们提出2-甲氧基雌二醇可能是通过硝基氧化应激依赖性机制调节癌细胞死亡和存活的天然调节剂。此外，结果证实了2-甲氧基雌二醇治疗神经母细胞瘤的有效性。
