title: Cytotoxicity of and DNA adduct formation by ellipticine and its micellar form in human leukemia cells in vitro.
abstract: OBJECTIVE
  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. 32P-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 µmol.L(-1) and 1.4±0.3 µmol.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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Stiborova
authors.affiliation: Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Manhartova
authors.affiliation: Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Hodek
authors.affiliation: Laboratory of Metallomics and Nanotechnology, Mendel University in Brno and Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Adam
authors.affiliation: Laboratory of Metallomics and Nanotechnology, Mendel University in Brno and Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
authors.forename: Rene
authors.initials: R
authors.lastname: Kizek
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Medical Faculty, Charles University and University Hospital Motol, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Eckschlager
authors.affiliation: Division of Preventive Oncology, National Center for Tumour Diseases, German Cancer Research Center, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Frei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018736:DNA Adducts / Q000187:drug effects*; D004611:Ellipticines / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects*; D008823:Micelles; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; D004611:Ellipticines; D008823:Micelles; C034192:ellipticine