Bak: A Downstream Mediator of Fenretinide-Induced Apoptosis of SH-SY5Y Neuroblastoma Cells

Penny E. Lovat, Serafina Oliverio, Marco Corazzari, Carlo Rodolfo, Marco Ranalli, Bojidar Goranov, Gerry Melino, Christopher P F Redfern, Mauro Piacentini

Research output: Contribution to journalArticle

Abstract

Unlike 13-cis-retinoic acid, the synthetic retinoid fenretinide [N-(4-hydroxyphenyl)retinamide] induces apoptosis of neuroblastoma cells by mechanisms involving retinoic acid receptors and oxidative stress. After screening a cDNA array for apoptosis-related genes, the Bcl2-related protein Bak was identified as a fenretinide-inducible gene in SH-SY5Y neuroblastoma cells, and this was confirmed by Western blotting and flow cytometry. Although fenretinide acts synergistically in vitro with chemotherapeutic drugs, these drugs did not induce Bak expression. Retinoic acid receptor antagonists did not block the induction of Bak by fenretinide. Conversely, Bak induction was blocked by the antioxidant vitamin C. Overexpression of Bak increased apoptosis in both the presence and absence of fenretinide, whereas expression of antisense Bak inhibited fenretinide-induced apoptosis. Bak expression was also induced in cells overexpressing the stress-induced transcription factor GADD153, but Bak expression was inhibited in cells expressing an antisense GADD153 construct. These results suggest that Bak is a downstream mediator of an oxidative stress pathway leading to apoptosis of SH-SY5Y neuroblastoma cells in response to fenretinide.

Original languageEnglish
Pages (from-to)7310-7313
Number of pages4
JournalCancer Research
Volume63
Issue number21
Publication statusPublished - Nov 1 2003

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Bak: A Downstream Mediator of Fenretinide-Induced Apoptosis of SH-SY5Y Neuroblastoma Cells'. Together they form a unique fingerprint.

  • Cite this

    Lovat, P. E., Oliverio, S., Corazzari, M., Rodolfo, C., Ranalli, M., Goranov, B., Melino, G., Redfern, C. P. F., & Piacentini, M. (2003). Bak: A Downstream Mediator of Fenretinide-Induced Apoptosis of SH-SY5Y Neuroblastoma Cells. Cancer Research, 63(21), 7310-7313.