Lookup NU author(s): Professor Penny Lovat,
Professor Archibald Malcolm,
Professor Andrew Pearson,
Dr Chris Redfern
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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.
Author(s): Lovat PE, Irving H, Annicchiarico-Petruzzelli M, Bernassola F, Malcolm AJ, Pearson ADJ, Melino G, Redfern CPF
Publication type: Article
Publication status: Published
Journal: European Journal of Cancer
Print publication date: 01/10/1997
ISSN (print): 0959-8049
ISSN (electronic): 1359-6349
PubMed id: 9516856
Altmetrics provided by Altmetric