Oncotarget

Research Papers:

DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol

Magdalena Gorska _, Alicja Kuban-Jankowska, Michal Zmijewski, Antonella Marino Gammazza, Francesco Cappello, Maciej Wnuk, Monika Gorzynik, Iwona Rzeszutek, Agnieszka Daca, Anna Lewinska and Michal Wozniak

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Oncotarget. 2015; 6:15449-15463. https://doi.org/10.18632/oncotarget.3913

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Abstract

Magdalena Gorska1, Alicja Kuban-Jankowska1, Michal Zmijewski2, Antonella Marino Gammazza3,4, Francesco Cappello3,4, Maciej Wnuk5, Monika Gorzynik1, Iwona Rzeszutek5, Agnieszka Daca6,7, Anna Lewinska8, Michal Wozniak1

1Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland

2Department of Histology, Medical University of Gdansk, Gdansk, Poland

3Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy ‘‘Emerico Luna’’, University of Palermo, Palermo, Italy

4Euro-Mediterranean Institute of Science and Technology, Palermo, Italy

5Department of Genetics, University of Rzeszow, Rzeszow, Poland

6Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland

7Department of Pathology and Experimental Rheumatology, Medical University of Gdansk, Gdansk, Poland

8Department of Biochemistry and Cell Biology, University of Rzeszow, Poland

Correspondence to:

Magdalena Gorska, e-mail: [email protected]

Keywords: 2-methoxyestradiol, neuronal nitric oxide synthase, reactive nitrogen species, nitric oxide, osteosarcoma

Received: February 10, 2015     Accepted: April 24, 2015     Published: May 06, 2015

ABSTRACT

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.


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