title: Sulindac sulfone modulates beta-catenin in human cholesteatoma cell culture.
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 micromol). 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 micromol sulindac sulfone, the average level of beta-catenin showed a decrease of 46% (0.004337 microg/mL) from those determined at 16 h with the same concentration of sulindac sulfone. At 800 micromol sulindac sulfone, the treated cell culture showed a reduction of 66.2% (0.003443 microg/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 micromol (minus 63%) and 800 micromol (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.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany. alexander.sauter@hno.uni-heidelberg.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Sauter
authors.forename: Rubina
authors.initials: R
authors.lastname: Matharu
authors.forename: Theresa
authors.initials: T
authors.lastname: Braun
authors.forename: Johannes
authors.initials: J
authors.lastname: Schultz
authors.forename: Haneen
authors.initials: H
authors.lastname: Sadick
authors.forename: Karl
authors.initials: K
authors.lastname: Hormann
authors.forename: Ramin
authors.initials: R
authors.lastname: Naim
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D002781:Cholesteatoma / Q000378:metabolism*; D004427:Ear Diseases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology; D051176:beta Catenin / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D051176:beta Catenin; D013467:Sulindac; C025463:sulindac sulfone