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

2015; Impact Journals LLC; Volume: 6; Issue: 17 Linguagem: Inglês

10.18632/oncotarget.3913

1949-2553

Magdalena Górska‐Ponikowska, Alicja Kuban‐Jankowska, Michał A. Żmijewski, Antonella Marino, Francesco Cappello, Maciej Wnuk, Monika Gorzynik-Debicka, Iwona Rzeszutek, Agnieszka Daca, Anna Lewińska, Michał Woźniak,

Electron Spin Resonance Studies

// Magdalena Gorska 1 , Alicja Kuban-Jankowska 1 , Michal Zmijewski 2 , Antonella Marino Gammazza 3, 4 , Francesco Cappello 3, 4 , Maciej Wnuk 5 , Monika Gorzynik 1 , Iwona Rzeszutek 5 , Agnieszka Daca 6, 7 , Anna Lewinska 8 , Michal Wozniak 1 1 Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland 2 Department of Histology, Medical University of Gdansk, Gdansk, Poland 3 Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy ''Emerico Luna'', University of Palermo, Palermo, Italy 4 Euro-Mediterranean Institute of Science and Technology, Palermo, Italy 5 Department of Genetics, University of Rzeszow, Rzeszow, Poland 6 Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland 7 Department of Pathology and Experimental Rheumatology, Medical University of Gdansk, Gdansk, Poland 8 Department of Biochemistry and Cell Biology, University of Rzeszow, Poland Correspondence to: Magdalena Gorska, e-mail: m.gorska@gumed.edu.pl 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.