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- Title
The biological activity of G-quadruplex DNA binding papaverine-derived ligand in breast cancer cells.
- Authors
Rubis, Blazej; Kaczmarek, Mariusz; Szymanowska, Natalia; Galezowska, Elzbieta; Czyrski, Andrzej; Juskowiak, Bernard; Hermann, Tadeusz; Rybczynska, Maria
- Abstract
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 (IC(50) for ligand 1 = 14.16 +/- 0.01 microM, 24 h, 1.158 +/- 0.056 microM, 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 microM 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 microM) inhibited telomerase activity as shown by TRAP assay.
- Publication
Investigational new drugs, 2009, Vol 27, Issue 4, p289
- ISSN
1573-0646
- Publication type
Journal Article
- DOI
10.1007/s10637-008-9173-9