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The role of gangliosides in fenretinide-induced apoptosis of neuroblastoma

Lookup NU author(s): Professor Penny Lovat, Dr Chris Redfern

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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. © 2005 Elsevier Ireland Ltd. All rights reserved.


Publication metadata

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

Publication type: Note

Publication status: Published

Journal: Cancer Letters

Year: 2005

Volume: 228

Issue: 1-2

Pages: 105-110

Print publication date: 18/10/2005

ISSN (print): 0304-3835

ISSN (electronic): 1872-7980

URL: http://dx.doi.org/10.1016/j.canlet.2005.01.044

DOI: 10.1016/j.canlet.2005.01.044

PubMed id: 15907365


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