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Effectiveness of human cytochrome P450 3A4 present in liposomal and microsomal nanoparticles in formation of covalent DNA adducts by ellipticine

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F16%3A10335709" target="_blank" >RIV/00216208:11310/16:10335709 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11130/16:10335709 RIV/00064203:_____/16:10335709 RIV/62156489:43210/16:43913034

  • Result on the web

  • DOI - Digital Object Identifier

Alternative languages

  • Result language

    angličtina

  • Original language name

    Effectiveness of human cytochrome P450 3A4 present in liposomal and microsomal nanoparticles in formation of covalent DNA adducts by ellipticine

  • Original language description

    OBJECTIVES: Ellipticine is an anticancer agent that functions through multiple mechanisms participating in cell cycle arrest and initiation of apoptosis. This drug forms covalent DNA adducts after its enzymatic activation with cytochrome P450 (CYP), which is one of the most important ellipticine DNA-damaging mechanisms of its cytotoxic effects. The improvements of cancer treatment are the major challenge in oncology research. Nanotransporters (nanoparticles) are promising approaches to target tumor cells, frequently leading to improve drug therapeutic index. Ellipticine has already been prepared in nanoparticle forms. However, since its anticancer efficiency depends on the CYP3A4-mediated metabolism in cancer cells, the aim of our research is to develop nanoparticles containing this enzyme that can be transported to tumor cells, thereby potentiating ellipticine cytotoxicity. METHODS: The CYP3A4 enzyme encapsulated into two nanoparticle forms, liposomes and microsomes, was tested to activate ellipticine to its reactive species forming covalent DNA adducts. Ellipticine-derived DNA adducts were determined by the 32P-postlabeling method. RESULTS: The CYP3A4 enzyme both in the liposome and microsome nanoparticle forms was efficient to activate ellipticine to species forming DNA adducts. Two DNA adducts, which are formed from ellipticine metabolites 12-hydroxy- and 13-hydroxyellipticine generated by its oxidation by CYP3A4, were formed by both CYP3A4 nanoparticle systems. A higher effectiveness of CYP3A4 in microsomal than in liposomal nanoparticles to form ellipticine-DNA adducts was found. CONCLUSION: Further testing in a suitable cancer cell model is encouraged to investigate whether the DNA-damaging effects of ellipticine after its activation by CYP3A4 nanoparticle forms are appropriate for active targeting of this enzyme to specific cancer cells.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    CE - Biochemistry

  • OECD FORD branch

Result continuities

  • Project

    <a href="/en/project/GA14-18344S" target="_blank" >GA14-18344S: Development of nanoparticle-based cytostatics and enzymes for enhanced chemotherapy of human neuroblastomas and study of mechanisms of their action</a><br>

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2016

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Neuroendocrinology Letters

  • ISSN

    0172-780X

  • e-ISSN

  • Volume of the periodical

    37

  • Issue of the periodical within the volume

    Suppl. 1

  • Country of publishing house

    SE - SWEDEN

  • Number of pages

    8

  • Pages from-to

    95-102

  • UT code for WoS article

  • EID of the result in the Scopus database