Publication detail

Expression Levels of Enzymes Metabolizing an Anticancer Drug Ellipticine Determined by Electromigration Assays Influence its Cytotoxicity to Cancer Cells - A Comparative Study

STIBOROVÁ, M. POLJAKOVÁ, J. MŘÍŽOVÁ, I. BOŘEK-DOHALSKÁ, L. ECKSCHLAGER, T. ADAM, V. KIZEK, R. FREI, E.

Original Title

Expression Levels of Enzymes Metabolizing an Anticancer Drug Ellipticine Determined by Electromigration Assays Influence its Cytotoxicity to Cancer Cells - A Comparative Study

Type

journal article in Web of Science

Language

English

Original Abstract

The antineoplastic alkaloid ellipticine is a prodrug, of which the pharmacological efficiency is dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to 12-hydroxy- and 13-hydroxyellipticine, which are both the metabolites forming DNA adducts in target tissues. Using the method of Western blotting, the expression of CYP1A1, 1B1, 3A4, lactoperoxidase, thyroid peroxidase, cyclooxygenase-1 and cytochrome b5, the enzymes that catalyze and/or influence ellipticine metabolism, was investigated in several cancer cells sensitive to ellipticine (HL-60 promyelocytic leukemia and T-cell leukemia CCRF-CEM cells, glioblastoma U87MG cells, thyroid cancer BHT-101, B-CPAP and 8505-C cells, neuroblastoma UKF-NB-3 and UKF-NB-4 cell lines and breast adenocarcinoma MCF-7 cells). The findings summarized from several former studies reviewed in this study, together with new results indicate that, depending on individual cells, cytotoxicity of ellipticine, which is mediated by formation of covalent DNA adducts to these cancer cells, is influenced by expression levels of these CYP and peroxidase enzymes in the tested cancer cells. Furthermore, a potency of ellipticine to induce the enzymes dictating activation of ellipticine to form DNA adducts in studied cancer cells determines an increase in cytotoxicity of ellipticine to these tumor cells.

Keywords

Ellipticine; Cancer Cells; Cytotoxicity; Cytochromes P450; Peroxidases; Protein Expression; Western Blotting; Metabolizmus; DNA adukty

Authors

STIBOROVÁ, M.; POLJAKOVÁ, J.; MŘÍŽOVÁ, I.; BOŘEK-DOHALSKÁ, L.; ECKSCHLAGER, T.; ADAM, V.; KIZEK, R.; FREI, E.

RIV year

2014

Released

1. 10. 2014

Publisher

ESG

ISBN

1452-3981

Periodical

INTERNATIONAL JOURNAL OF ELECTROCHEMICAL SCIENCE

Year of study

9

Number

10

State

Republic of Serbia

Pages from

5675

Pages to

5689

Pages count

15

URL

http://www.electrochemsci.org/papers/vol9/91005675.pdf

Full text in the Digital Library

http://hdl.handle.net/11012/201461

BibTex

@article{BUT112440,
  author="Marie {Stiborová} and Jitka {Poljaková} and Iveta {Mřížová} and Lucie {Bořek-Dohalská} and Tomáš {Eckschlager} and Vojtěch {Adam} and René {Kizek} and Eva {Frei}",
  title="Expression Levels of Enzymes Metabolizing an Anticancer Drug Ellipticine Determined by Electromigration Assays Influence its Cytotoxicity to Cancer Cells - A Comparative Study",
  journal="INTERNATIONAL JOURNAL OF ELECTROCHEMICAL SCIENCE",
  year="2014",
  volume="9",
  number="10",
  pages="5675--5689",
  issn="1452-3981",
  url="http://www.electrochemsci.org/papers/vol9/91005675.pdf"
}