title: In vitro induction of apoptosis and necrosis by new derivatives of daunorubicin.
abstract: OBJECTIVE
  The comparative effects of daunorubicin, and its new formamidine derivatives containing either a morpholine moiety (DAUFmor) or a hexamethyleneimine moiety (DAUFhex) in the amidine group, on induction of programmed cell death were determined.
  
  
  METHODS
  The experiments were performed on human acute lymphoblastic leukemia MOLT-4 cells and human acute myeloblastic leukemia ML-1 cells. The research was conducted using the flow cytometry annexin V-fluorescein (FITC)/propidium iodide (PI) method and tetramethylrhodamine ethyl ester (TMRE) assay.
  
  
  RESULTS
  The various patterns of temporary changes of early apoptotic cells, late apoptotic and necrotic cells, and in the frequency of the acute leukemia cells with high values of mitochondrial membrane potential (MMP) were found. Phosphatidylserine externalization, plasma membrane disruption, and changes in MMP occurring in the leukemia cells were dependent on the agent tested, its concentration, the time intervals after daunorubicin, DAUFmor, and DAUFhex application, and on the leukemia cell line used.
  
  
  CONCLUSIONS
  The structural modifications of daunorubicin producing two new analogs, DAUFmor and DAUFhex, induced the different responses of MOLT-4 and ML-1 cells to triggering of programmed death.
authors.affiliation: D.Sc., Department of Experimental Hematology, Jagiellonian University, Gronostajowa 9, 30-387 Cracow, Poland. lidia.mazur@uj.edu.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Stojak
authors.forename: Lidia
authors.initials: L
authors.lastname: Mazur
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Opydo-Chanek
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Lukawska
authors.forename: Irena
authors.initials: I
authors.lastname: Oszczapowicz
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009336:Necrosis
chemical_list: D000903:Antibiotics, Antineoplastic; C584766:DAUFhex compound; C584765:DAUFmor compound; D003630:Daunorubicin
keywords: Daunorubicin derivatives; apoptosis; human acute leukemia cells; mitochondrial membrane potential; necrosis