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

Leuk Res. 2012 Jun;36(6):791-8. doi: 10.1016/j.leukres.2012.02.017. Epub 2012 Mar 13.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneugens / administration & dosage
  • Aneugens / pharmacology
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / pharmacology
  • Cell Cycle / drug effects*
  • Cell Death / drug effects
  • Cell Proliferation / drug effects
  • DNA Fragmentation / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Leukemia / drug therapy
  • Leukemia / metabolism*
  • Leukemia / pathology*
  • Osmolar Concentration
  • Polyploidy
  • Reactive Oxygen Species / metabolism*
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Aneugens
  • Antibiotics, Antineoplastic
  • Reactive Oxygen Species
  • Doxorubicin