HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

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.
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
Topics
  • 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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: