Publication detail

Cytotoxicity of and DNA adduct formation by ellipticine and its micellar form in human leukemia cells in vitro

STIBOROVÁ, M. MANHARTOVÁ, Z. HODEK, P. ADAM, V. KIZEK, R. ECKSCHLAGER, T. FREI, E.

Original Title

Cytotoxicity of and DNA adduct formation by ellipticine and its micellar form in human leukemia cells in vitro

Type

journal article in Web of Science

Language

English

Original Abstract

OBJECTIVES: The improvements of cancer treatment are the major challenge in oncology research. Nanocarriers are one of the promising approaches to selectively target tumor cells, frequently leading to improve drug therapeutic index. Ellipticine is an anticancer agent that functions through multiple mechanisms. Here, the toxic effects of an anticancer drug ellipticine encapsulated in a micellar nanotransporter and free ellipticine on human HL-60 leukemia cells and formation of ellipticine-derived DNA adducts by both forms of the drug in these cells were investigated. METHODS: The toxicity of modified ellipticine on cells was compared to that of free ellipticine using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide cytotoxicity assay. P-32-postlabeling was utilized to determine ellipticine-DNA adducts in treated cells. RESULTS: The comparison of efficiencies of free ellipticine and ellipticine-micelles [the poly(ethylene oxide)-block-poly(allyl glycidyl ether) block copolymer] to form ellipticine-derived DNA adducts in leukemia HL-60 cells and to act as cytotoxic agent on these cells was performed. Exposure of HL-60 cells to ellipticine in micelles resulted in formation of ellipticine-DNA adducts and caused the cytotoxic effect on these cells. The influence of ellipticine in micelles on HL-60 cells was very similar to that of free ellipticine. The ellipticine half maximal inhibition concentration was determined as 1.3+/-0.3 mu mol.L-1 and 1.4+/-0.3 mu mol.L-1 for ellipticine and ellipticine in micelles, respectively. Likewise, the levels of ellipticine-DNA adducts generated in HL-60 cells by both forms of ellipticine were analogous. CONCLUSION: The results found in this work demonstrate similar cytotoxicity and DNA-damaging effects of ellipticine and its micellar form on leukemia HL-60 cells in vitro.

Keywords

ellipticine; nanoparticles; micelles; cytotoxicity; leukemia HL-60 cells; ellipticine-derived DNA adducts; P-32-postlabeling

Authors

STIBOROVÁ, M.; MANHARTOVÁ, Z.; HODEK, P.; ADAM, V.; KIZEK, R.; ECKSCHLAGER, T.; FREI, E.

Released

1. 1. 2015

ISBN

0172-780X

Periodical

NEUROENDOCRINOLOGY LETTERS

Year of study

36

Number

1

State

Kingdom of Sweden

Pages from

22

Pages to

28

Pages count

7

BibTex

@article{BUT145344,
  author="STIBOROVÁ, M. and MANHARTOVÁ, Z. and HODEK, P. and ADAM, V. and KIZEK, R. and ECKSCHLAGER, T. and FREI, E.",
  title="Cytotoxicity of and DNA adduct formation by ellipticine and its micellar form in human leukemia cells in vitro",
  journal="NEUROENDOCRINOLOGY LETTERS",
  year="2015",
  volume="36",
  number="1",
  pages="22--28",
  issn="0172-780X"
}