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

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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

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Authors and Affiliations

  1. Northern Institute for Cancer Research and School of Clinical Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK

    Q. D. Campbell Hewson, P. E. Lovat, J. B. Catterall & C. P. F. Redfern

  2. INMI-IRCCS Lazzaro Spallanzani, Rome, 00149, Italy

    M. Corazzari

  3. Northern Institute for Cancer Research, Medical School, University of Newcastle, Paul O’Gorman Building, Newcastle upon Tyne, NE2 4HH, UK

    C. P. F. Redfern

Authors
  1. Q. D. Campbell Hewson
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  2. P. E. Lovat
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  3. M. Corazzari
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  4. J. B. Catterall
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  5. C. P. F. Redfern
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Corresponding author

Correspondence to C. P. F. Redfern.

Additional information

This work was supported by The North of England Children’s Cancer Research Fund and CLIC.

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Hewson, Q.D.C., Lovat, P.E., Corazzari, M. et al. The NF-κB pathway mediates fenretinide-induced apoptosis in SH-SY5Y neuroblastoma cells. Apoptosis 10, 493–498 (2005). https://doi.org/10.1007/s10495-005-1878-z

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