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

Lookup NU author(s): Professor Penny Lovat, Dr Michael Tilby, Professor Archibald Malcolm, Professor Andrew Pearson, Dr Chris Redfern

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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.


Publication metadata

Author(s): Lovat, P.E., Ranalli, M., Bernassola, F., Tilby, M., Malcolm, A.J., Pearson, A.D.J., Piacentini, M., Melino, G., Redfern, C.P.F.

Publication type: Article

Publication status: Published

Journal: Medical and Pediatric Oncology

Year: 2000

Volume: 35

Issue: 6

Pages: 663-668

Print publication date: 01/01/2000

ISSN (print): 1545-5009

ISSN (electronic): 1545-5017

URL: http://dx.doi.org/10.1002/1096-911X(20001201)35:6<663::AID-MPO39>3.0.CO;2-4

DOI: 10.1002/1096-911X(20001201)35:6<663::AID-MPO39>3.0.CO;2-4

PubMed id: 11107142


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