These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The novel anticancer drug oracin: different stereospecificity and cooperativity for carbonyl reduction by purified human liver 11beta-hydroxysteroid dehydrogenase type 1.
    Author: Wsól V, Szotáková B, Skálová L, Maser E.
    Journal: Toxicology; 2004 May 03; 197(3):253-61. PubMed ID: 15033547.
    Abstract:
    Inherent or acquired resistance of tumor cells to anti-cancer drugs is a problem of major importance in chemotherapy. In addition to detailed research into the mechanisms of drug inactivation, attention has also been paid to the synthesis of new structures. Oracin is a promising cytostatic drug, which is presently in phase II of clinical trials. This investigation was designed to characterize the metabolic inactivation of oracin by carbonyl reduction to 11-dihydrooracin (DHO). We identified 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) as the principal enzyme being responsible for oracin carbonyl reduction in human liver microsomes. The purified 11beta-HSD 1 catalyses this reaction in a stereospecific manner. Formation of (-)-DHO surpasses that of (+)-DHO by a factor of around four. Moreover, 11beta-HSD 1 exhibits enzyme cooperativity for the formation of both enantiomers (Hill coefficients of 2.26 +/- 0.20 and 1.84 +/- 0.29 for (-)-DHO and (+)-DHO, respectively). Comparing the differences in the stereospecificity and Hill coefficients between the microsomes and purified 11beta-HSD 1 could anticipate contribution of another microsomal enzyme. In case of oracin, this enzyme cooperativity may become important with respect to maximal plasma concentrations, and, by inhibition of 11beta-HSD 1, to enhance the chemotherapeutic efficacy of this anti-cancer drug.
    [Abstract] [Full Text] [Related] [New Search]