Daunorubicin-induced variations in gene transcription: commitment to proliferation arrest, senescence and apoptosis

Biochem J. 2003 Jun 15;372(Pt 3):703-11. doi: 10.1042/BJ20021950.


We used a human cDNA macroarray containing various oncogenes and tumour suppressor genes to assess gene expression profiles in early-passage Jurkat T lymphocytes treated with clinically relevant concentrations of the antitumour antibiotic daunorubicin. Several oncogenes and tumour suppressor genes were either up- or down-regulated depending on the daunorubicin concentration used. The expression levels of some of these genes were confirmed by semi-quantitative reverse transcriptase-PCR. We also compared the changes in cell-cycle distribution and the apoptotic morphological characteristics of the cells treated with daunorubicin, using flow cytometry and fluorescence microscopy. Exposure to 182 nM daunorubicin (its IC(75) in Jurkat T cells: where IC(75) is the drug concentration that inhibits growth by 75%) resulted in cell-cycle arrest in G(1) and almost immediate apoptosis. In contrast, decreasing the drug concentration to 91 nM (close to the IC(50)) caused G(2) arrest and cell senescence-like growth arrest, whereas features of apoptosis and necrosis appeared only after longer incubation times. Gene expression profiles, cell-cycle distribution, the presence of DNA damage and the time-dependent response of Jurkat T cells to cell death were correlated clearly. The general behaviour of the genes suggests that cell-cycle arrest and cell death follow distinct pathways depending on drug concentration.

Publication types

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

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects*
  • Cellular Senescence / drug effects*
  • DNA, Complementary / genetics
  • Daunorubicin / pharmacology*
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • G2 Phase / drug effects
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Genes, Tumor Suppressor / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Jurkat Cells
  • Microscopy, Fluorescence
  • Oligonucleotide Array Sequence Analysis
  • Oncogenes / drug effects
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / physiology
  • Transcription, Genetic / drug effects*


  • Antibiotics, Antineoplastic
  • DNA, Complementary
  • Daunorubicin