Investigational New Drugs

, Volume 27, Issue 4, pp 289–296 | Cite as

The biological activity of G-quadruplex DNA binding papaverine-derived ligand in breast cancer cells

  • Blazej Rubis
  • Mariusz Kaczmarek
  • Natalia Szymanowska
  • Elzbieta Galezowska
  • Andrzej Czyrski
  • Bernard Juskowiak
  • Tadeusz Hermann
  • Maria RybczynskaEmail author


It was shown previously that the papaverine oxidation products 6a,12a-diazadibenzo-[a,g]fluorenylium derivative (ligand 1) and 2,3,9,10-tetramethoxy-12-oxo-12H-indolo[2,1-a]isoquinolinium chloride (ligand 2) bind to guanine-quadruplexes (G4) of single stranded G-rich 3′-overhangs of mammalian telomeric DNA. Here we show the biological activity of ligand 1. This compound exhibit antiproliferative activity in MCF-7 cells (IC50 for ligand 1 = 14.16 ± 0.01 μM, 24 h, 1.158 ± 0.056 μM, 72 h. PCNA levels were not altered after treatment of MCF-7 cells with concentrations of ligand 1 which, however, led to alterations in the cell cycle. 5 and 10 μM of the ligand 1 arrested cells in the G0/G1 phase of the cell cycle and this led to a decrease of cells in the S phase. Intracellular accumulation of ligand 1 was observed even after a cell passage and medium exchange in fluorescence microscopy while low concentrations of ligand 1 (0.001 to 0.1 μM) inhibited telomerase activity as shown by TRAP assay.


Papaverine derivative Cell cycle arrest Breast cancer Telomerase inhibitor DNA binding G-quadruplex DNA 



The present study was supported by the Joint Research Grant from Adam Mickiewicz University and Poznan University of Medical Sciences, Poznan, Poland and by N N401 223 534 research grant.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Blazej Rubis
    • 1
  • Mariusz Kaczmarek
    • 2
  • Natalia Szymanowska
    • 1
  • Elzbieta Galezowska
    • 3
  • Andrzej Czyrski
    • 4
  • Bernard Juskowiak
    • 3
  • Tadeusz Hermann
    • 4
  • Maria Rybczynska
    • 1
    Email author
  1. 1.Department of Clinical Chemistry and Molecular DiagnosticsPoznan University of Medical SciencesPoznanPoland
  2. 2.Department of Clinical ImmunologyPoznan University of Medical SciencesPoznanPoland
  3. 3.Laboratory of Analytical Chemistry, Faculty of ChemistryAdam Mickiewicz University in PoznanPoznanPoland
  4. 4.Department of Physical Pharmacy and PharmacokineticsPoznan University of Medical SciencesPoznanPoland

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