Neuronal Nitric Oxide Synthase Induction in the Antitumorigenic and Neurotoxic Effects of 2-Methoxyestradiol

Molecules

Magdalena Gorska²  Alicja Kuban-Jankowska²  Michal Aleksander Zmijewski¹  Monika Gorzynik²  Michal Szkatula² 

[1] Department of Histology, Medical University of Gdansk, Gdansk 80-211, Poland; E-Mail:;Department of Medical Chemistry, Medical University of Gdansk, Gdansk 80-211, Poland; E-Mails:

关键词: osteosarcoma;    hippocampus;    cancer;    neurodegenerative disease;    2-methoxyestradiol;    neuronal nitric oxide synthase;    3-nitrotyrosine;   

DOI  :  10.3390/molecules190913267

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.