Molecular mechanisms of fenretinide-induced apoptosis of neuroblastoma cells

Penny E. Lovat, Marco Corazzari, Bojidar Goranov, Mauro Piacentini, C. P F Redfern

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)81-89
Number of pages9
JournalAnnals of the New York Academy of Sciences
Publication statusPublished - 2004


  • Apoptosis
  • Fenretinide
  • Neuroblastoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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