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

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

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Abstract

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.


Publication metadata

Author(s): Irving, H., Lovat, P.E., Campbell-Hewson, Q., Malcolm, A., Pearson, A.D.J., Redfern, C.P.F.

Publication type: Article

Publication status: Published

Journal: European Journal of Cancer

Year: 1998

Volume: 34

Issue: 1

Pages: 111-117

Print publication date: 01/01/1998

ISSN (print): 0959-8049

ISSN (electronic): 1359-6349

URL: http://dx.doi.org/10.1016/S0959-8049(97)10027-2

DOI: 10.1016/S0959-8049(97)10027-2

PubMed id: 9624247


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