title: DNA strand breaks induced by nuclear hijacking of neuronal NOS as an anti-cancer effect of 2-methoxyestradiol.
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.
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gorska
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Kuban-Jankowska
authors.affiliation: Department of Histology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Zmijewski
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy ''Emerico Luna'', University of Palermo, Palermo, Italy.|Euro-Mediterranean Institute of Science and Technology, Palermo, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Marino Gammazza
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy ''Emerico Luna'', University of Palermo, Palermo, Italy.|Euro-Mediterranean Institute of Science and Technology, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cappello
authors.affiliation: Department of Genetics, University of Rzeszow, Rzeszow, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Wnuk
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Gorzynik
authors.affiliation: Department of Genetics, University of Rzeszow, Rzeszow, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Rzeszutek
authors.affiliation: Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland.|Department of Pathology and Experimental Rheumatology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Daca
authors.affiliation: Department of Biochemistry and Cell Biology, University of Rzeszow, Rzeszow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lewinska
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Wozniak
mesh_terms: D000077584:2-Methoxyestradiol; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D048749:Cytokinesis / Q000187:drug effects; D053960:DNA Breaks / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D012516:Osteosarcoma / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D026361:Reactive Nitrogen Species / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; D026361:Reactive Nitrogen Species; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D009569:Nitric Oxide; D004958:Estradiol; D000077584:2-Methoxyestradiol; D052248:Nitric Oxide Synthase Type I
keywords: 2-methoxyestradiol; neuronal nitric oxide synthase; nitric oxide; osteosarcoma; reactive nitrogen species