title: Subcellular localization of proflavine derivative and induction of oxidative stress--in vitro studies.
abstract: Acridines have been studied for several decades because of their numerous biological effects, especially anticancer activity. Recently, cytotoxicity of novel acridine derivatives, 3,6-bis((1-alkyl-5-oxo-imidazolidin-2-yliden)imino)acridine hydrochlorides (AcrDIMs), was confirmed for leukemic cell lines [Bioorg. Med. Chem.2011, 19, 1790]. The mechanism of action of the most cytotoxic hexyl-AcrDIM was studied in this paper focusing attention on a subcellular distribution of the drug. Accumulation of hexyl-AcrDIM in mitochondria was confirmed after labeling mitochondria with MitoRED using ImageStream Imaging Flow Cytometer. The derivative significantly decreased intracellular ATP level (reduction of ATP level was decreased by vitamin E), and induced oxidative stress (ROS production detected by DHE assay) as well as cell cycle arrest in the S-phase (flow cytometry analysis) already after short-time incubation and induction of apoptosis. Cytotoxicity of hexyl-AcrDIM is closely connected with induction of oxidative stress in cells.
authors.affiliation: Department of Chemical and Biochemical Engineering, Faculty of Chemical and Food Technology, Slovak Technical University, Radlinského 9, 812 37 Bratislava, Slovak Republic. Electronic address: ipothova.zuzana@gmail.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Ipóthová
authors.forename: H
authors.initials: H
authors.lastname: Paulíková
authors.forename: L
authors.initials: L
authors.lastname: Cižeková
authors.forename: L
authors.initials: L
authors.lastname: Hunáková
authors.forename: M
authors.initials: M
authors.lastname: Labudová
authors.forename: A
authors.initials: A
authors.lastname: Grolmusová
authors.forename: L
authors.initials: L
authors.lastname: Janovec
authors.forename: J
authors.initials: J
authors.lastname: Imrich
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000187:drug effects*; D011370:Proflavine / Q000031:analogs & derivatives / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000166:Acridines; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D011370:Proflavine
keywords: Acridine; Anticancer; Mitochondria