title: The differential influence of non-iodinated and mono- or diiodinated benzoic acids on cellular and nuclear uptake of the nuclear localization sequence of the SV 40 T antigen.
abstract: We synthesized several novel compounds to evaluate the different effects of non-iodinated and mono- or diiodinated benzoic acid on the cellular and nuclear uptake of the SV 40 T antigen nuclear localization sequence (NLS) in human LN18 and U373 glioma cells. The skeletal structure of all the conjugates contained the fluorescein isothiocyanate (FITC)-labeled NLS of the SV 40T antigen, to which either benzoic acid, mono- or diiodobenzoic acid was coupled. As shown by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS), the basic FITC-labeled NLS alone was taken up by the nuclei of only a few glioma cells which remained intact. The coupling of non-iodinated benzoic acid (BA) did not result in a markedly larger number of nuclearly stained cells. A very marked increase in cells with nuclear staining was found with the conjugate containing monoiodobenzoic acid (MIBA). This was also associated with a high cell death rate. Similar results were obtained with the conjugate containing diiodobenzoic acid (DIBA). However, coincubation with free mono- or diiodobenzoic acid and the basic FITC-labeled NLS did not result in a marked change in the number of strongly stained cells or cell viability compared to the results of incubation with the FITC-labeled NLS alone. Surprisingly, FITC-labeled MIBA- and DIBA-conjugates containing a scrambled SV 40 T antigen NLS were also taken up by the cell nuclei of LN18 and U373 glioma cells and led to cell death. Such mono- or diiodobenzoic acid conjugates may therefore have potential in the development of new non-radioactive drugs against malignant glioma cells.
authors.affiliation: Department of Neuroradiology, University of Tübingen, Germany. stefan.heckl@med.uni-tuebingen.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Heckl
authors.forename: Alexander
authors.initials: A
authors.lastname: Sturzu
authors.forename: Marc
authors.initials: M
authors.lastname: Regenbogen
authors.forename: Alexander
authors.initials: A
authors.lastname: Beck
authors.forename: Alireza
authors.initials: A
authors.lastname: Gharabaghi
authors.forename: Hartmut
authors.initials: H
authors.lastname: Echner
mesh_terms: D017304:Annexin A5 / Q000737:chemistry; D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry / Q000378:metabolism*; D001565:Benzoates / Q000737:chemistry*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D018613:Microscopy, Confocal; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D017304:Annexin A5; D000952:Antigens, Polyomavirus Transforming; D001565:Benzoates; D005456:Fluorescent Dyes; D016650:Fluorescein-5-isothiocyanate