Retinoid-induced differentiation of neuroblastoma: Comparison between LG69, an RXR-selective analogue and 9-cis retinoic acid

The aim of this study was to investigate in vitro the effects of all-trans retinoic acid (RA), 9-cis RA and the RXR-selective analogue, LG69, on the morphological differentiation, proliferation and gene expression of neuroblastoma cells. Three different cell lines were cultured with the retinoid for...

Full description

Saved in:
Bibliographic Details
Published in:European journal of cancer (1990) 1998-01, Vol.34 (1), p.111-117
Main Authors: Irving, H, Lovat, P.E, Campbell Hewson, Q, Malcolm, A.J, Pearson, A.D.J, Redfern, C.P.F
Format: Article
Language:English
Subjects:
9-cis retinoic acid
Antineoplastic agents
Antineoplastic Agents - pharmacology
apoptosis
Bexarotene
Biological and medical sciences
Blotting, Northern
Cell Differentiation - drug effects
Cell Division - drug effects
Chemotherapy
differentiation
Dose-Response Relationship, Drug
Gene Expression
Humans
Medical sciences
neuroblastoma
Neuroblastoma - pathology
Pharmacology. Drug treatments
proliferation
retinoid
Tetrahydronaphthalenes - pharmacology
Tretinoin - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The aim of this study was to investigate in vitro the effects of all-trans retinoic acid (RA), 9-cis RA and the RXR-selective analogue, LG69, on the morphological differentiation, proliferation and gene expression of neuroblastoma cells. Three different cell lines were cultured with the retinoid for either 9 continuous days or for 5 days followed by 4 days without the retinoid and morphological differentiation was assessed both qualitatively and quantitatively. SH SY 5Y cell proliferation was examined by measuring cell numbers after exposure to the retinoids and RAR-β gene expression was examined by Northern blot analysis. Morphological differentiation was more effectively induced by all-trans and 9-cis RA than by LG69. SH SY 5Y cells, when treated with 9-cis RA for only 5 of the 9 days of culture, underwent apoptosis, but this was not seen with 9 days continuous exposure nor with LG69. Inhibition of SH SY 5Y cell proliferation by all-trans or 9-cis RA was dose-dependent, but LG69 had little effect. Conversely, LG69 induced higher expression of RAR-β than all-trans RA, but less than that produced by 9-cis RA. These data suggest that 9-cis RA as a single agent is the most effective modulator of neuroblastoma behaviour and may be the most appropriate therapeutic agent.
ISSN:0959-8049
1879-0852
DOI:10.1016/S0959-8049(97)10027-2