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Cell-cycle disturbance and induction of programmed death by new formamidine analogs of daunorubicin.

AbstractBACKGROUND/AIM:
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.
MATERIALS AND 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.
CONCLUSION:
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.
AuthorsMarta Stojak, Małgorzata Lukawska, Irena Oszczapowicz, Małgorzata Opydo-Chanek, Lidia Mazur
JournalAnticancer research (Anticancer Res) Vol. 34 Issue 12 Pg. 7151-8 (Dec 2014) ISSN: 1791-7530 [Electronic] Greece
PMID25503143 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Chemical References
  • Antibiotics, Antineoplastic
  • DAUFhex compound
  • DAUFmor compound
  • DNA
  • Daunorubicin
Topics
  • Antibiotics, Antineoplastic (pharmacology)
  • Apoptosis (drug effects)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • DNA (genetics)
  • DNA Fragmentation (drug effects)
  • Daunorubicin (analogs & derivatives, pharmacology)
  • Flow Cytometry
  • Humans
  • M Phase Cell Cycle Checkpoints (drug effects)
  • Necrosis (pathology)
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma (pathology)

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