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The apoptotic action of the retinoid CD437/AHPN: Diverse effects, common basis

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  • Published:
Journal of Biomedical Science

Abstract

Retinoids, such as all-trans-retinoic acid (RA), have found applications in several different types of (cancer) therapies. The synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437 or AHPN), an RA receptor (RAR)γ agonist, not only induces RARγ-dependent differentiation, but in contrast to RA, it also induces RARγ-independent apoptosis in many tumor cells. This observation makes this and similar new retinoids very interesting from a clinical perspective. Several genes have been associated with CD437/AHPN-mediated apoptosis, but the multiple activities of this compound and the apparent cell-type-specific responses to treatment have made it difficult to discern a common biochemical basis for the mechanism of its apoptotic action. In this brief review, we present a model which links all CD437/AHPN-associated apoptotic effects. CD437/AHPN rapidly induces DNA adduct formation through an as-yet unknown reaction which is independent of cell type. This is followed by a cell-type-specific, largely p53-independent DNA damage response which can result in engagement of multiple cell death pathways and activation of caspases as a common endpoint. At the same time, the RARγ-dependent pathway leads to regulation of differentiation-associated, cell-type-specific genes. CD437/AHPN, with its simultaneous differentiation and apoptosis-inducing activities, is a good prototype for new drugs which may be clinically more efficacious than those with a single activity.

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Authors and Affiliations

  1. Department of Otolaryngology, Boston University School of Medicine, Boston, Mass., USA

    Xiansi Zhao & Remco A. Spanjaard

  2. Cancer Research Center, Boston University School of Medicine, 02118, Boston, MA, USA

    Remco A. Spanjaard

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  1. Xiansi Zhao
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Zhao, X., Spanjaard, R.A. The apoptotic action of the retinoid CD437/AHPN: Diverse effects, common basis. J Biomed Sci 10, 44–49 (2003). https://doi.org/10.1007/BF02255996

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