Retinoids in neuroblastoma therapy: distinct biological properties of 9-cis- and all-trans-retinoic acid.

We investigated the potential for 9-cis-retinoic acid in the differentiation therapy of neuroblastoma using an N-type neuroblastoma cell line, SH SY 5Y, as an experimental model. In these cells, 9-cis-retinoic acid is more effective than other isomers at inducing the expression of RAR-beta. An RAR-alpha-specific antagonist inhibited the induction of RAR-beta in response to all-trans-but not to 9-cis-retinoic acid. This indicates that the mechanism of gene induction by 9-cis-retinoic acid differs markedly from all-trans-retinoic acid. 9-cis-retinoic acid is also better than all-trans at producing sustained morphological differentiation and inhibition of proliferation of SH SY 5Y cells. Although N-type neuroblastoma cells are not thought to undergo apoptosis in response to all-trans-retinoic acid, we observed a significant degree of apoptosis in SH SY 5Y cells treated with 9-cis-retinoic acid for 5 days and then cultured in the absence of retinoid, an effect not observed in cells treated with the all-trans isomer. These results suggest that 9-cis- and all-trans-retinoic acid have distinct biological properties and that 9-cis retinoic acid may be clinically effective in neuroblastoma by inducing both differentiation and apoptosis under an appropriate treatment regimen.
AuthorsP E Lovat, H Irving, M Annicchiarico-Petruzzelli, F Bernassola, A J Malcolm, A D Pearson, G Melino, C P Redfern
JournalEuropean journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 33 Issue 12 Pg. 2075-80 (Oct 1997) ISSN: 0959-8049 [Print] ENGLAND
PMID9516856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Benzoates
  • Chromans
  • Receptors, Retinoic Acid
  • retinoic acid receptor alpha
  • retinoic acid receptor beta
  • Ro 41-5253
  • alitretinoin
  • Tretinoin
  • Antineoplastic Agents (therapeutic use)
  • Apoptosis (drug effects)
  • Benzoates (pharmacology)
  • Cell Differentiation (drug effects)
  • Cell Division (drug effects)
  • Chromans (pharmacology)
  • Drug Screening Assays, Antitumor
  • Humans
  • Neuroblastoma (drug therapy, metabolism, pathology)
  • Receptors, Retinoic Acid (antagonists & inhibitors, metabolism)
  • Tretinoin (therapeutic use)
  • Tumor Cells, Cultured (drug effects)

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