The NF-kappaB pathway mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells.
Apoptosis
; 10(3): 493-8, 2005 May.
Article
em En
| MEDLINE
| ID: mdl-15909111
ABSTRACT
Fenretinide induces apoptosis in SH-SY5Y neuroblastoma cells via a signaling pathway involving the production of reactive oxygen species (ROS), 12-lipoxygenase activity and the induction of the GADD153 transcription factor. NF-kappa B is a key element of many cell signaling pathways and adopts a pro- or anti-apoptotic role in different cell types. Studies have suggested that NF-kappa B may play a pro-apoptotic role in SH-SY5Y cells, and in other cell types NF-kappa B activation may be linked to lipoxygenase activity. The aim of this study was to test the hypothesis that NF-kappa B activity mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells. Using a dominant-negative construct for Ikappa Balpha stably transfected into SH-SY5Y cells, we show that apoptosis, but not the induction of ROS, in response to fenretinide was blocked by abrogation of NF-kappa B activity. In parental SH-SY5Y cells, fenretinide induced NF-kappa B activity and Ikappa Balpha phosphorylation. These results suggest that NF-kappa B activity links fenretinide-induced ROS to the induction of apoptosis in SH-SH5Y cells, and may be a target for the future development of drugs for neuroblastoma therapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
/
Fenretinida
/
Apoptose
Limite:
Humans
Idioma:
En
Revista:
Apoptosis
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Reino Unido