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.
Keywords:
2-methoxyestradiol; neuronal nitric oxide synthase; nitric oxide; osteosarcoma; reactive nitrogen species.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Methoxyestradiol
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Bone Neoplasms / pathology
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Cell Line, Tumor
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Cytokinesis / drug effects
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DNA Breaks / drug effects*
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Estradiol / analogs & derivatives*
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Estradiol / pharmacology
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G2 Phase Cell Cycle Checkpoints / drug effects
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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M Phase Cell Cycle Checkpoints / drug effects
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase Type I / genetics*
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Osteosarcoma / pathology*
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Oxidative Stress / drug effects
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Reactive Nitrogen Species / metabolism
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Tumor Suppressor p53-Binding Protein 1
Substances
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Antineoplastic Agents
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Intracellular Signaling Peptides and Proteins
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Reactive Nitrogen Species
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TP53BP1 protein, human
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Tumor Suppressor p53-Binding Protein 1
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Nitric Oxide
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Estradiol
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2-Methoxyestradiol
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Nitric Oxide Synthase Type I