title: Distinct properties of fenretinide and CD437 lead to synergistic responses with chemotherapeutic reagents.
abstract: The RARbeta/gamma-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 RARbeta/gamma-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.
authors: Department of Child Health, University of Newcastle, Newcastle Upon Tyne, United Kingdom.
authors: P E
authors: PE
authors: Lovat
authors: M
authors: M
authors: Ranalli
authors: F
authors: F
authors: Bernassola
authors: M
authors: M
authors: Tilby
authors: A J
authors: AJ
authors: Malcolm
authors: A D
authors: AD
authors: Pearson
authors: M
authors: M
authors: Piacentini
authors: G
authors: G
authors: Melino
authors: C P
authors: CP
authors: Redfern
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002648:Child; D004357:Drug Synergism; D017313:Fenretinide / Q000627:therapeutic use*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012176:Retinoids / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C099555:CD 437; D005609:Free Radicals; D012176:Retinoids; D017313:Fenretinide