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

被引：30

作者：

Gorska, Magdalena ^{[1
]}

Kuban-Jankowska, Alicja ^{[1
]}

Zmijewski, Michal ^{[2
]}

Gammazza, Antonella Marino ^{[3
,4
]}

Cappello, Francesco ^{[3
,4
]}

Wnuk, Maciej ^{[5
]}

Gorzynik, Monika ^{[1
]}

Rzeszutek, Iwona ^{[5
]}

Daca, Agnieszka ^{[6
,7
]}

Lewinska, Anna ^{[8
]}

Wozniak, Michal ^{[1
]}

机构：

[1] Med Univ Gdansk, Dept Med Chem, Gdansk, Poland

[2] Med Univ Gdansk, Dept Histol, Gdansk, Poland

[3] Univ Palermo, Sect Human Anat Emerico Luna, Dept Expt Biomed & Clin Neurosci, Palermo, Italy

[4] Euromediterranean Inst Sci & Technol, Palermo, Italy

[5] Univ Rzeszow, Dept Genet, Rzeszow, Poland

[6] Med Univ Gdansk, Dept Pathophysiol, Gdansk, Poland

[7] Med Univ Gdansk, Dept Pathol & Expt Rheumatol, Gdansk, Poland

[8] Univ Rzeszow, Dept Biochem & Cell Biol, Rzeszow, Poland

来源：

ONCOTARGET | 2015年 / 6卷 / 17期

关键词：

2-methoxyestradiol; neuronal nitric oxide synthase; reactive nitrogen species; nitric oxide; osteosarcoma; NITRIC-OXIDE SYNTHASE; CELL-CYCLE ARREST; REACTIVE OXYGEN; CANCER-CELLS; IN-VITRO; ORAL; 2-METHOXYESTRADIOL; ESTROGEN METABOLITE; CARCINOMA-CELLS; GLIOMA-CELLS; PHASE-II;

D O I：

10.18632/oncotarget.3913

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

2-Methoxyestradiol (2-ME) is a physiological metabolite of 17 beta- 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.

引用

页码：15449 / 15463

页数：15

共 101 条

[1] Nitric oxide synthases: structure, function and inhibition [J].