Toggle Main Menu Toggle Search

Open Access padlockePrints

Molecular mechanisms of fenretinide-induced apoptosis of neuroblastoma cells

Lookup NU author(s): Professor Penny Lovat, Bojidar Goranov, Dr Chris RedfernORCiD


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Synthetic retinoids such as fenretinide [N-(4-hydroxyphenyl)retinamide] induce apoptosis of neuroblastoma cells, act synergistically with chemotherapeutic drugs, and may provide opportunities for novel approaches to neuroblastoma therapy. Fenretinide-induced cell death of neuroblastoma cells is caspase dependent and results in the release of cytochrome c from mitochondria independently of changes in permeability transition. This is mediated by a signaling pathway characterized by the generation of reactive oxygen species (ROS) via 12-lipoxygenase (12-LOX), and an oxidative-stress-dependent induction of the transcription factor, GADD153 and the BCL2-related protein BAK. Upstream events of fenretinide-induced signaling involve increased levels of ceramide as a result of increased sphingomyelinase activity, and the subsequent metabolism of ceramide to gangliosides via glucosylceramide synthase and GD3 synthase. These gangliosides may be involved in the regulation of 12-LOX leading to oxidative stress and apoptosis via the induction of GADD153 and BAK. The targeting of sphingomyelinases or downstream effectors such as 12-LOX or GADD153 may present novel approaches for the development of more effective and selective drugs for neuroblastoma therapy. © 2004 New York Academy of Sciences.

Publication metadata

Author(s): Lovat, P.E., Corazzari, M., Goranov, B., Piacentini, M., Redfern, C.P.F.

Publication type: Article

Publication status: Published

Journal: Annals of the New York Academy of Sciences

Year: 2004

Volume: 1028

Pages: 81-89

Print publication date: 01/01/2004

ISSN (print): 0077-8923

ISSN (electronic): 1749-6632


DOI: 10.1196/annals.1322.009

PubMed id: 15650234


Altmetrics provided by Altmetric