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