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Sulindac sulfone modulates β-Catenin in human cholesteatoma cell culture
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Sauter, Alexander, Matharu, Rubina, Braun, Theresa, Schultz, Johannes, Sadick, Haneen, Hormann, Karl and Naim, Ramin (2007) Sulindac sulfone modulates β-Catenin in human cholesteatoma cell culture. Archives of Medical Research, Vol.38 (No.4). pp. 367-371. doi:10.1016/j.arcmed.2006.11.005 ISSN 0188-4409.
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Official URL: http://dx.doi.org/10.1016/j.arcmed.2006.11.005
Abstract
Background. External auditory canal cholesteatoma (EACC) is a chronic inflammation of the bony ear meatus. Its etiology is not clearly understood. Other than surgical intervention, conservative methods are investigated for different cholesteatomas. Inducing apoptosis seems to be an appropriate strategy. Sulindac sulfone is a new class of targeted and pro-apoptotic drugs. It provokes apoptosis by inducing phosphorylation of beta-catenin, which is a multifunctional protein in the cell-cell adhesion complex.
Methods. EACC-cell cultures were incubated with different concentrations of sulindac sulfone (400 and 800 mu mol). After 16, 24, and 48 h, beta-catenin concentrations were determined by ELISA, Western blot, and immunohistochemical analysis.
Results. After 48 h incubation with 400 mu mol sulindac sulfone, the average level of beta-catenin showed a decrease of 46% (0.004337 mu g/mL) from those determined at 16 h with the same concentration of sulindac sulfone. At 800 mu mol sulindac sulfone, the treated cell culture showed a reduction of 66.2% (0.003443 mu g/mL). Comparing total protein content and the fraction of beta-catenin at different points in time, the concentration of beta-catenin decreased in both EACC cell cultures, 400 mu mol (minus 63%) and 800 mu mol (minus 81%).
Conclusions. The results presented in this paper are the first to demonstrate the chemopreventive effects of the agent sulindac sulfone on cholesteatomas. The greatest decrease of beta-catenin was observed between 16 and 24 h incubation. The inhibitory effect of sulindac sulfone as a local treatment seems to be a useful additional tool for nonsurgical approach to the therapy of EACCs. (C) 2007 IMSS. Published by Elsevier Inc.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
Journal or Publication Title: | Archives of Medical Research | ||||
Publisher: | Elsevier | ||||
ISSN: | 0188-4409 | ||||
Official Date: | May 2007 | ||||
Dates: |
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Volume: | Vol.38 | ||||
Number: | No.4 | ||||
Number of Pages: | 5 | ||||
Page Range: | pp. 367-371 | ||||
DOI: | 10.1016/j.arcmed.2006.11.005 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
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