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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
NICLOSAMIDE CHANGES THE CELL MEMBRANE PROPERTIES OF THE CACO-2 BARRIER MODEL
Abstract number: P139
Lornejad-Schäfer
1
*M.R.
, Schäfer
1
C., Schröder
1
K.R.
1
BioMed-zet Life Science GmbH, Linz, Austria
Question:
Niclosamide has been used long as a drug against tapeworm. Recently, it is studied as drug against colon cancer metastasis. The aim of this study was to find out how is the effect of niclosamide on the cell membrane properties, membrane integrity and permeability in the differentiated Caco-2 barrier model?
Methods:
Caco-2 cells seeded onto inserts were differentiated for 21 days, followed by niclosamide treatment for 24 h. The morphology of cells was investigated using microscopy analysis. The rate of cell cytotoxicity of niclosamide was determined using LDH assay. The cell transepithelial electrical resistance (TER) was measured using impedance (Z) measurement. The membrane permeability was tested by selective transport of small Fluorescein thiocarbamoyl (FITC)-dextran (3-5 kDa).
Results and Discussion:
Niclosamide at a concentration above 25 µM changed the cell morphology and dose-dependently increased the rate of cytotoxicity in the differentiated Caco-2 cells. The TER value was reduced at concentrations between 5-10 µM (not cytotoxic dose). The dose-dependently decrease of TER value (=membrane integrity) correlated significantly with increasing permeability of small molecules, FITC-dextran (3-5 kDa). Therefore, we assume that niclosamide affected the paracellular transport pathway due to changing of tight junction protein complexes which are required for the maintenance of surface membrane integrity. The investigation of niclosamide effect on the tight junction proteins is our ongoing research.
Conclusion:
The administration of niclosamide in the therapeutic dose range about 200 mg pro patient (Varam et.al. 1990) equivalent to 10 µM in vitro may increase the permeability of other co-administered substances (drug or diet) due to changing the cell membrane properties of an intestinal barrier model.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P139