Neuronal Nitric Oxide Synthase Induction in the Antitumorigenic and Neurotoxic Effects of 2-methoxyestradiol

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2014 Aug 30

PMID 25170949

Citations 12

Authors

Magdalena Gorska

Alicja Kuban-Jankowska

Michal Aleksander Zmijewski

Monika Gorzynik

Michal Szkatula

Michal Wozniak

Affiliations

Soon will be listed here.

Abstract

Objective: 2-Methoxyestradiol, one of the natural 17β-estradiol derivatives, is a novel, potent anticancer agent currently being evaluated in advanced phases of clinical trials. The main goal of the study was to investigate the anticancer activity of 2-methoxy-estradiol towards osteosarcoma cells and its possible neurodegenerative effects. We used an experimental model of neurotoxicity and anticancer activity of the physiological agent, 2-methoxyestradiol. Thus, we used highly metastatic osteosarcoma 143B and mouse immortalized hippocampal HT22 cell lines. The cells were treated with pharmacological (1 μM, 10 μM) concentrations of 2-methoxyestradiol.

Experimental: Neuronal nitric oxide synthase and 3-nitrotyrosine protein levels were determined by western blotting. Cell viability and induction of cell death were measured by MTT and PI/Annexin V staining and a DNA fragmentation ELISA kit, respectively. Intracellular levels of nitric oxide were determined by flow cytometry.

Results: Here we demonstrated that the signaling pathways of neurodegenerative diseases and cancer may overlap. We presented evidence that 2-methoxyestradiol, in contrast to 17β-estradiol, specifically affects neuronal nitric oxide synthase and augments 3-nitrotyrosine level leading to osteosarcoma and immortalized hippocampal cell death.

Conclusions: We report the dual facets of 2-methoxyestradiol, that causes cancer cell death, but on the other hand may play a key role as a neurotoxin.

Citing Articles

Endogenous estrogen metabolites as oxidative stress mediators and endometrial cancer biomarkers.

Bukato K, Kostrzewa T, Marino Gammazza A, Gorska-Ponikowska M, Sawicki S Cell Commun Signal. 2024; 22(1):205.

PMID: 38566107 PMC: 10985914. DOI: 10.1186/s12964-024-01583-0.

2-Methoxyestradiol Damages DNA in Glioblastoma Cells by Regulating nNOS and Heat Shock Proteins.

Bastian P, Daca A, Ploska A, Kuban-Jankowska A, Kalinowski L, Gorska-Ponikowska M Antioxidants (Basel). 2022; 11(10).

PMID: 36290736 PMC: 9598669. DOI: 10.3390/antiox11102013.

Regulation of Mitochondrial Dynamics in Parkinson's Disease-Is 2-Methoxyestradiol a Missing Piece?.

Bastian P, Dulski J, Roszmann A, Jacewicz D, Kuban-Jankowska A, Slawek J Antioxidants (Basel). 2021; 10(2).

PMID: 33562035 PMC: 7915370. DOI: 10.3390/antiox10020248.

Regulation of mitochondrial dynamics in 2-methoxyestradiol-mediated osteosarcoma cell death.

Gorska-Ponikowska M, Bastian P, Zauszkiewicz-Pawlak A, Ploska A, Zubrzycki A, Kuban-Jankowska A Sci Rep. 2021; 11(1):1616.

PMID: 33452331 PMC: 7811003. DOI: 10.1038/s41598-020-80816-x.

Modification of DNA structure by reactive nitrogen species as a result of 2-methoxyestradiol-induced neuronal nitric oxide synthase uncoupling in metastatic osteosarcoma cells.

Gorska-Ponikowska M, Ploska A, Jacewicz D, Szkatula M, Barone G, Lo Bosco G Redox Biol. 2020; 32:101522.

PMID: 32305006 PMC: 7162974. DOI: 10.1016/j.redox.2020.101522.

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