Adriamycin dose and time effects on cell cycle, cell death, and reactive oxygen species generation in leukaemia cells

Abstract We investigate the relative importance of the different mechanisms of Adriamycin, an anthracycline, and their interrelations, in particular the link between cell cycle arrest, cell death, and generation of reactive oxygen species (ROS) that is suspected to be the origin of cardiotoxic side-...

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Bibliographic Details
Published in:Leukemia research 2012-06, Vol.36 (6), p.791-798
Main Authors: Savatier, Julien, Rharass, Tareck, Canal, Christophe, Gbankoto, Adam, Vigo, Jean, Salmon, Jean-Marie, Ribou, Anne-Cécile
Format: Article
Language:English
Subjects:
Adriamycin
Aneugens - administration & dosage
Aneugens - pharmacology
Anthracycline
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - pharmacology
Apoptosis
Cell cycle
Cell Cycle - drug effects
Cell death
Cell Death - drug effects
Cell Proliferation - drug effects
Cytosol
DNA Fragmentation - drug effects
Dose-Response Relationship, Drug
Doxorubicin - administration & dosage
Doxorubicin - pharmacology
Fluorescence
Hematology, Oncology and Palliative Medicine
Humans
Inhibitory Concentration 50
Leukemia
Leukemia - drug therapy
Leukemia - metabolism
Leukemia - pathology
Mitochondria
Multiparametric analysis
Nuclei
Osmolar Concentration
Polyploid cells
Polyploidy
Reactive oxygen species
Reactive Oxygen Species - metabolism
Side effects
Time Factors
Tumor Cells, Cultured
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Summary:Abstract We investigate the relative importance of the different mechanisms of Adriamycin, an anthracycline, and their interrelations, in particular the link between cell cycle arrest, cell death, and generation of reactive oxygen species (ROS) that is suspected to be the origin of cardiotoxic side-effects. We introduced a lifetime fluorescence based technology and used videomicrofluorometry, two efficient analytical methods. We show that depending on the doses and time after incubation, ADR will not reach the same compartments (nucleus, mitochondria, cytosol) in the cells, having consequences on the production of ROS, growth arrest pathways and cell death pathways.
ISSN:0145-2126
1873-5835
DOI:10.1016/j.leukres.2012.02.017