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Ellipticine cytotoxicity to cancer cell lines — a comparative study

Ellipticine is a potent antineoplastic agent exhibiting multiple mechanisms of action. This anticancer agent should be considered a pro-drug, whose pharmacological efficiency and/or genotoxic side effects are dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to species fo...

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Autores principales: Stiborová, Marie, Poljaková, Jitka, Martínková, Eva, Bořek-Dohalská, Lucie, Eckschlager, Tomáš, Kizek, Rene, Frei, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Slovak Toxicology Society SETOX 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131681/
https://www.ncbi.nlm.nih.gov/pubmed/21753906
http://dx.doi.org/10.2478/v10102-011-0017-7
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author Stiborová, Marie
Poljaková, Jitka
Martínková, Eva
Bořek-Dohalská, Lucie
Eckschlager, Tomáš
Kizek, Rene
Frei, Eva
author_facet Stiborová, Marie
Poljaková, Jitka
Martínková, Eva
Bořek-Dohalská, Lucie
Eckschlager, Tomáš
Kizek, Rene
Frei, Eva
author_sort Stiborová, Marie
collection PubMed
description Ellipticine is a potent antineoplastic agent exhibiting multiple mechanisms of action. This anticancer agent should be considered a pro-drug, whose pharmacological efficiency and/or genotoxic side effects are dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to species forming covalent DNA adducts. Ellipticine can also act as an inhibitor or inducer of biotransformation enzymes, thereby modulating its own metabolism leading to its genotoxic and pharmacological effects. Here, a comparison of the toxicity of ellipticine to human breast adenocarcinoma MCF-7 cells, leukemia HL-60 and CCRF-CEM cells, neuroblastoma IMR-32, UKF-NB-3 and UKF-NB-4 cells and U87MG glioblastoma cells and mechanisms of its action to these cells were evaluated. Treatment of all cells tested with ellipticine resulted in inhibition of cell growth and proliferation. This effect was associated with formation of two covalent ellipticine-derived DNA adducts, identical to those formed by 13-hydroxy- and 12-hydroxyellipticine, the ellipticine metabolites generated by CYP and peroxidase enzymes, in MCF-7, HL-60, CCRF-CEM, UKF-NB-3, UKF-NB-4 and U87MG cells, but not in neuroblastoma UKF-NB-3 cells. Therefore, DNA adduct formation in most cancer cell lines tested in this comparative study might be the predominant cause of their sensitivity to ellipticine treatment, whereas other mechanisms of ellipticine action also contribute to its cytotoxicity to neuroblastoma UKF-NB-3 cells.
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spelling pubmed-31316812011-07-13 Ellipticine cytotoxicity to cancer cell lines — a comparative study Stiborová, Marie Poljaková, Jitka Martínková, Eva Bořek-Dohalská, Lucie Eckschlager, Tomáš Kizek, Rene Frei, Eva Interdiscip Toxicol Original Article Ellipticine is a potent antineoplastic agent exhibiting multiple mechanisms of action. This anticancer agent should be considered a pro-drug, whose pharmacological efficiency and/or genotoxic side effects are dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to species forming covalent DNA adducts. Ellipticine can also act as an inhibitor or inducer of biotransformation enzymes, thereby modulating its own metabolism leading to its genotoxic and pharmacological effects. Here, a comparison of the toxicity of ellipticine to human breast adenocarcinoma MCF-7 cells, leukemia HL-60 and CCRF-CEM cells, neuroblastoma IMR-32, UKF-NB-3 and UKF-NB-4 cells and U87MG glioblastoma cells and mechanisms of its action to these cells were evaluated. Treatment of all cells tested with ellipticine resulted in inhibition of cell growth and proliferation. This effect was associated with formation of two covalent ellipticine-derived DNA adducts, identical to those formed by 13-hydroxy- and 12-hydroxyellipticine, the ellipticine metabolites generated by CYP and peroxidase enzymes, in MCF-7, HL-60, CCRF-CEM, UKF-NB-3, UKF-NB-4 and U87MG cells, but not in neuroblastoma UKF-NB-3 cells. Therefore, DNA adduct formation in most cancer cell lines tested in this comparative study might be the predominant cause of their sensitivity to ellipticine treatment, whereas other mechanisms of ellipticine action also contribute to its cytotoxicity to neuroblastoma UKF-NB-3 cells. Slovak Toxicology Society SETOX 2011-06 2011-06 /pmc/articles/PMC3131681/ /pubmed/21753906 http://dx.doi.org/10.2478/v10102-011-0017-7 Text en Copyright © 2011 Slovak Toxicology Society SETOX http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Stiborová, Marie
Poljaková, Jitka
Martínková, Eva
Bořek-Dohalská, Lucie
Eckschlager, Tomáš
Kizek, Rene
Frei, Eva
Ellipticine cytotoxicity to cancer cell lines — a comparative study
title Ellipticine cytotoxicity to cancer cell lines — a comparative study
title_full Ellipticine cytotoxicity to cancer cell lines — a comparative study
title_fullStr Ellipticine cytotoxicity to cancer cell lines — a comparative study
title_full_unstemmed Ellipticine cytotoxicity to cancer cell lines — a comparative study
title_short Ellipticine cytotoxicity to cancer cell lines — a comparative study
title_sort ellipticine cytotoxicity to cancer cell lines — a comparative study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131681/
https://www.ncbi.nlm.nih.gov/pubmed/21753906
http://dx.doi.org/10.2478/v10102-011-0017-7
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