Neuronal nitric oxide synthase induction in the antitumorigenic and neurotoxic effects of 2-methoxyestradiol.
Molecules
; 19(9): 13267-81, 2014 Aug 28.
Article
en En
| MEDLINE
| ID: mdl-25170949
ABSTRACT
OBJECTIVE:
2-Methoxyestradiol, one of the natural 17ß-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 17ß-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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Estradiol
/
Óxido Nítrico Sintasa de Tipo I
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Año:
2014
Tipo del documento:
Article