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A new class of retinoids with selective inhibition of AP-1 inhibits proliferation

Nature volume 372, pages 107–111 (1994)Cite this article

Abstract

RETINOIDS regulate many biological processes, including differen-tiation, morphogenesis and cell proliferation1–3. They are also important therapeutic agents, but their clinical usefulness is limited because of side effects4–8. Retinoid activities are mediated by speci-fic nuclear receptors, the RARs and RXRs, which can induce tran-scriptional activation through specific DNA sites3,9–11 or by inhibiting the transcription factor AP-1 (refs 12–15), which usually mediates cell proliferation signals16. Because the two types of receptor actions are mechanistically distinct12, 15, we investigated whether conformationally restricted retinoids, selective for each type of receptor action, could be identified. Here we describe a new class of retinoids that selectively inhibits AP-1 activity but does not activate transcription. These retinoids do not induce differentiation in F9 cells but inhibit effectively the proliferation of several tumour cell lines, and could thus serve as candidates for new retinoid therapeutic agents with reduced side effects.

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Author information

Affiliations

  1. Cancer Center, La Jolla Cancer Research Foundation, La Jolla, California, 92037, USA

    Andrea Fanjul, Marcia I. Dawson, Peter D. Hobbs, Ling Jong, James F. Cameron, Eli Harlev, Gerhart Graupner, Xian-Ping Lu & Magnus Pfahl

  2. Life Sciences Division, SRI International, Menlo Park, California, 94025, USA

    Marcia I. Dawson, Peter D. Hobbs, Ling Jong, James F. Cameron & Eli Harlev

Authors
  1. Andrea Fanjul
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  2. Marcia I. Dawson
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  3. Peter D. Hobbs
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  4. Ling Jong
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  5. James F. Cameron
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  6. Eli Harlev
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  7. Gerhart Graupner
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  8. Xian-Ping Lu
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  9. Magnus Pfahl
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Fanjul, A., Dawson, M., Hobbs, P. et al. A new class of retinoids with selective inhibition of AP-1 inhibits proliferation. Nature 372, 107–111 (1994). https://doi.org/10.1038/372107a0

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