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: Stefan Heckl, Alexander Sturzu, Marc Regenbogen, Alexander Beck, Alireza Gharabaghi, Hartmut Echner
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 355 Issue 1-2 Pg. 131-40 (May 01 2008) ISSN: 0378-5173 [Print] Netherlands
• PMID: 18249512 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A5
• Antigens, Polyomavirus Transforming
• Benzoates
• Fluorescent Dyes
• Fluorescein-5-isothiocyanate

Topics

• Annexin A5 (chemistry)
• Antigens, Polyomavirus Transforming (chemistry, metabolism)
• Benzoates (chemistry)
• Cell Line
• Cell Nucleus (metabolism)
• Cell Survival
• Flow Cytometry
• Fluorescein-5-isothiocyanate
• Fluorescent Dyes
• Humans
• Microscopy, Confocal
• Spectrometry, Mass, Electrospray Ionization