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

Lookup NU author(s): Professor Penny Lovat, Professor Archibald Malcolm, Professor Andrew Pearson, Dr Chris Redfern

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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.


Publication metadata

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

Year: 1997

Volume: 33

Issue: 12

Pages: 2075-2080

Print publication date: 01/10/1997

ISSN (print): 0959-8049

ISSN (electronic): 1359-6349

Publisher: Pergamon

URL: http://dx.doi.org/10.1016/S0959-8049(97)00242-6

DOI: 10.1016/S0959-8049(97)00242-6

PubMed id: 9516856


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