Distinct properties of fenretinide and CD437 lead to synergistic responses with chemotherapeutic reagents

Penny E. Lovat, Marco Ranalli, Francesca Bernassola, Mike Tilby, Archie J. Malcolm, Andy D J Pearson, Mauro Piacentini, Gerry Melino, Christopher P F Redfern

Research output: Contribution to journalArticlepeer-review

Abstract

The RARβ/γ-selective retinoids fenretinide and CD437 induce caspase-dependent apoptosis but generate free radicals independently of caspases. Apoptosis, but not free radical generation, induced by these retinoids is inhibited by RARβ/γ-specific antagonists. Both fenretinide and CD437 induce apoptosis synergistically with cisplatin, carboplatin, or etoposide. However, antioxidants inhibit this synergy to the level obtained with chemotherapeutic drugs alone, and this implies that free radical generation is important in the synergistic response. Since apoptosis induced by fenretinide or CD437 is mediated by apoptotic pathways involving RARs and/or mitochondria and differs from mechanisms of chemotherapy-induced apoptosis this may explain the strong synergistic response seen between these synthetic retinoids and chemotherapeutic drugs. These results suggest that fenretinide or CD437 may be useful adjuncts to neuroblastoma therapy. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)663-668
Number of pages6
JournalMedical and Pediatric Oncology
Volume35
Issue number6
DOIs
Publication statusPublished - 2000

Keywords

  • CD437
  • Chemotherapy
  • Fenretinide

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Cancer Research

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