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  • The apoptotic action of the retinoid CD437/AHPN: diverse effects, common basis
  • Zhao X; Spanjaard RA
  • J Biomed Sci 2003[Jan]; 10 (1): 44-9
  • 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)gamma agonist, not only induces RARgamma-dependent differentiation, but in contrast to RA, it also induces RARgamma-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 RARgamma-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.
  • |Antineoplastic Agents/pharmacology[MESH]
  • |Apoptosis/*drug effects[MESH]
  • |Cell Differentiation/drug effects/genetics[MESH]
  • |DNA Adducts[MESH]
  • |DNA Damage/drug effects[MESH]
  • |Gene Expression Regulation/drug effects[MESH]
  • |Humans[MESH]
  • |Retinoids/metabolism/*pharmacology[MESH]
  • |Signal Transduction/drug effects[MESH]

  • *{{pmid12566985}}
    *<b>[ The apoptotic action of the retinoid CD437/AHPN: diverse effects, common basis ]</b> J Biomed Sci 2003; 10(1) ; 44-9 Zhao X; Spanjaard RA


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    J Biomed Sci

    44 1.10 2003