title: Cell-cycle disturbance and induction of programmed death by new formamidine analogs of daunorubicin.
abstract: OBJECTIVE
  Structural modifications of daunorubicin are an important way to change its anticancer activity. For this reason, formamidinodaunorubicins have been synthesized. The present study was undertaken to determine and compare the in vitro effects of daunorubicin and its new formamidine derivatives on human acute leukemia MOLT-4 and ML-1 cells.
  
  
  METHODS
  The experiments were performed on human acute lymphoblastic leukemia MOLT-4 cells and human acute myeloblastic leukemia ML-1 cells. The study was conducted using flow cytometry and light microscopy methods.
  
  
  RESULTS
  The various patterns of temporary changes in the cell cycle and DNA fragmentation, as well as the extent of mitotic catastrophe, apoptosis, and necrosis, were determined. The anti-leukemic activities of the new daunorubicin analogs were weaker than that of daunorubicin.
  
  
  CONCLUSIONS
  The influence of these anthracyclines on cell-cycle progression, DNA damage, and induction of mitotic catastrophe and cell death depended on the agent and its concentration, the time interval after application, and the cell line used. The structural modifications of daunorubicin were responsible for the different cytotoxic effects of the two formamidinodaunorubicins.
authors.affiliation: Department of Experimental Hematology, Jagiellonian University in Kraków, Kraków, Poland marta.stojak@uj.edu.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Stojak
authors.affiliation: Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, Warszawa, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Lukawska
authors.affiliation: Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, Warszawa, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Oszczapowicz
authors.affiliation: Department of Experimental Hematology, Jagiellonian University in Kraków, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Opydo-Chanek
authors.affiliation: Department of Experimental Hematology, Jagiellonian University in Kraków, Kraków, Poland.
authors.forename: Lidia
authors.initials: L
authors.lastname: Mazur
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D009336:Necrosis / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*
chemical_list: D000903:Antibiotics, Antineoplastic; C584766:DAUFhex compound; C584765:DAUFmor compound; D004247:DNA; D003630:Daunorubicin
keywords: Cell cycle; DNA strand breaks; daunorubicin; formamidinodaunorubicins; mitotic catastrophe; programmed cell death