The role of gangliosides in fenretinide-induced apoptosis of neuroblastoma

Penny E. Lovat, Marco Corazzari, Federica Di Sano, Mauro Piacentini, C. P F Redfern

Research output: Contribution to journalArticlepeer-review

Abstract

Fenretinide is thought to induce apoptosis via increases in ceramide levels but the mechanisms of ceramide generation and the link between ceramide and subsequent apoptosis in neuroblastoma cells is unclear. In SH-SY5Y neuroblastoma cells, evidence suggests that acid sphingomyelinase activity is essential for the induction of ceramide and apoptosis in response to fenretinide. Downstream of ceramide, apoptosis in response to fenretinide is mediated by increased glucosylceramide synthase activity resulting in increased levels of gangliosides GD3 and GD2 via GD3 synthase. GD3 is a key signalling intermediate leading to apoptosis via the activation of 12-Lipoxygenase, and the parallel induction of GD2 suggests that fenretinide might enhance the response of neuroblastoma to therapy with anti-GD2 antibodies.

Original languageEnglish
Pages (from-to)105-110
Number of pages6
JournalCancer Letters
Volume228
Issue number1-2
DOIs
Publication statusPublished - Oct 18 2005

Keywords

  • Apoptosis
  • Ceramide
  • Fenretinide
  • Gangliosides
  • GD2
  • GD3

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

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