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9-cis retinoic acid — a better retinoid for the modulation of differentiation, proliferation and gene expression in human neuroblastoma

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Abstract

To date, the clinical success of 13-cis or all-trans retinoic acid in the treatment of neuroblastoma has been disappointing. In vivo, 13-cis will isomerise to both all-trans and 9-cis retinoic acid, believed to be the main biologically-active isomers. In vitro studies with an N-type neuroblastoma cell line, SH SY 5Y, show that 9-cis is better than other isomers at both inducing morphological differentiation and inhibiting proliferation. RAR-β, a gene which may mediate retinoic acid responsiveness and be of prognostic significance, is also more-effectively induced by 9-cis retinoic acid. 9-cis and all-trans retinoic acid do not have synergistic effects on SH SY 5Y cell proliferation and gene expression. A retinoid X receptor (RXR)-specific analogue of 9-cis retinoic acid had similar effects on gene expression to 9-cis retinoic acid alone. In view of these results, 9-cis retinoic acid or stable analogues of this retinoid may have potential for the treatment of neuroblastoma.

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Authors and Affiliations

  1. Departments of Medicine (Medical Molecular Biology Group), UK

    Christopher P.F. Redfern

  2. Child Health, UK

    Penny E. Lovat, Helen Irving & Andrew D.J. Pearson

  3. Pathology, University of Newcastle upon Tyne, NE2 4HH, UK

    Archie J. Malcolm

Authors
  1. Penny E. Lovat
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  2. Helen Irving
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  3. Archie J. Malcolm
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  4. Andrew D.J. Pearson
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  5. Christopher P.F. Redfern
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Lovat, P.E., Irving, H., Malcolm, A.J. et al. 9-cis retinoic acid — a better retinoid for the modulation of differentiation, proliferation and gene expression in human neuroblastoma. J Neurooncol 31, 85–91 (1997). https://doi.org/10.1023/A:1005785431343

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