Fenretinide: A p53-independent way to kill cancer cells

Marco Corazzari, Penny E. Lovat, Serafina Oliverio, Federica Di Sano, Raffaele Perrone Donnorso, Christopher P F Redfern, Mauro Piacentini

Research output: Contribution to journalArticle

Abstract

The synthetic retinoid fenretinide [N-(4 hydroxyphenyl)retinamide] induces apoptosis of cancer cells and acts synergistically with chemotherapeutic drugs, thus providing opportunities for novel approaches to cancer therapy. The upstream signaling events induced by fenretinide include an increase in intracellular levels of ceramide, which is subsequently metabolized to GD3. This ganglioside triggers the activation of 12-Lox (12-lipoxygenase) leading to oxidative stress and apoptosis via the induction of the transcription factor Gadd153 and the Bcl-2-family member protein Bak. Increased evidence suggests that the apoptotic pathway activated by fenretinide is p53-independent and this may represent a novel way to treat tumors resistant to DNA-damaging chemotherapeutic agents. Therefore, fenretinide offers increased clinical benefit as a novel agent for cancer therapy, able to complement the action of existing chemotherapeutic treatment regimes. Furthermore, synergy between fenretinide and chemotherapeutic drugs may facilitate the use of chemotherapeutic drugs at lower concentrations, with possible reduction in treatment-associated morbidity.

Original languageEnglish
Pages (from-to)810-815
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume331
Issue number3
DOIs
Publication statusPublished - Jun 10 2005

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Keywords

  • Ceramide
  • Gadd153
  • GD3
  • Glucosylceramide synthase
  • Retinoids

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Corazzari, M., Lovat, P. E., Oliverio, S., Di Sano, F., Donnorso, R. P., Redfern, C. P. F., & Piacentini, M. (2005). Fenretinide: A p53-independent way to kill cancer cells. Biochemical and Biophysical Research Communications, 331(3), 810-815. https://doi.org/10.1016/j.bbrc.2005.03.184