Apoptosis

, Volume 10, Issue 3, pp 493–498 | Cite as

The NF-κB pathway mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells

  • Q. D. Campbell Hewson
  • P. E. Lovat
  • M. Corazzari
  • J. B. Catterall
  • C. P. F. Redfern
Article

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-κ 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-κ B may play a pro-apoptotic role in SH-SY5Y cells, and in other cell types NF-κ B activation may be linked to lipoxygenase activity. The aim of this study was to test the hypothesis that NF-κ B activity mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells. Using a dominant-negative construct for Iκ Bα 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-κ B activity. In parental SH-SY5Y cells, fenretinide induced NF-κ B activity and Iκ Bα phosphorylation. These results suggest that NF-κ 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

Keywords

apoptosis fenretinide neuroblastoma NF-κ B retinoic acid 

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Q. D. Campbell Hewson
    • 1
  • P. E. Lovat
    • 1
  • M. Corazzari
    • 2
  • J. B. Catterall
    • 1
  • C. P. F. Redfern
    • 1
    • 3
  1. 1.Northern Institute for Cancer Research and School of Clinical Medical SciencesUniversity of Newcastle upon TyneNewcastle upon TyneUK
  2. 2.INMI-IRCCS Lazzaro SpallanzaniRomeItaly
  3. 3.Northern Institute for Cancer Research, Medical SchoolUniversity of NewcastleNewcastle upon TyneUK

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