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

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-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.

• Authors: P E Lovat, H Irving, M Annicchiarico-Petruzzelli, F Bernassola, A J Malcolm, A D Pearson, G Melino, C P Redfern
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 33 Issue 12 Pg. 2075-80 (Oct 1997) ISSN: 0959-8049 [Print] England
• PMID: 9516856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzoates
• Chromans
• RARA protein, human
• Receptors, Retinoic Acid
• Retinoic Acid Receptor alpha
• retinoic acid receptor beta
• Ro 41-5253
• Alitretinoin
• Tretinoin

Topics

• Alitretinoin
• 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)
• Retinoic Acid Receptor alpha
• Tretinoin (therapeutic use)
• Tumor Cells, Cultured (drug effects)