title: The biological activity of G-quadruplex DNA binding papaverine-derived ligand in breast cancer cells.
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.
authors.affiliation: Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Blazej
authors.initials: B
authors.lastname: Rubis
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kaczmarek
authors.forename: Natalia
authors.initials: N
authors.lastname: Szymanowska
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Galezowska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Czyrski
authors.forename: Bernard
authors.initials: B
authors.lastname: Juskowiak
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Hermann
authors.forename: Maria
authors.initials: M
authors.lastname: Rybczynska
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D054856:G-Quadruplexes; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008856:Microscopy, Fluorescence; D010084:Oxidation-Reduction; D010208:Papaverine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors
chemical_list: D008024:Ligands; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA; D010208:Papaverine; D019098:Telomerase
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