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

P. E. Lovat, H. Irving, M. Annicchiarico-Petruzzelli, F. Bernassola, A. J. Malcolm, A. D J Pearson, G. Melino, C. P F Redfern

Research output: Contribution to journalArticle

Abstract

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-β. An RAR-α-specific antagonist inhibited the induction of RAR-β 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.

Original languageEnglish
Pages (from-to)2075-2080
Number of pages6
JournalEuropean Journal of Cancer
Volume33
Issue number12
DOIs
Publication statusPublished - Oct 1997

Keywords

  • 9-cis-retinoic acid
  • Apoptosis
  • Differentiation
  • Neuroblastoma
  • RAR
  • Receptors
  • Retinoids

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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