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The effect of the NF-kappa B inhibitors curcumin and lactacystin on myogenic differentiation of rhabdomyosarcoma cells.
MedLine Citation:
PMID:  22469857     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Rhabdomyosarcoma is a soft tissue sarcoma mainly seen in children. Despite considerable progress within the last few years, therapeutic approaches for this type of tumor are still limited. The respective tumor cells originate from myogenic precursor cells and are characterized by a blockade in their differentiation program. Interestingly, there is a direct inverse correlation between the differentiation status of a specific rhabdomyosarcoma cell and its metastatic potential. Thus, here, we tested whether the ubiquitous transcription factor NF-κB, which regulates myogenic differentiation and is also a promising therapeutic target in the treatment of other types of tumors, might be an interesting candidate for the development of novel rhabdomyosarcoma treatment strategies. For this purpose, we analyzed NF-κB activity (classical pathway) in myoblasts with different differentiation potential, specifically in three different rhabdomyosarcoma cell lines. In addition, we inhibited NF-κB activity in these cells and analyzed the effects on myogenic differentiation. We show that after the induction of differentiation, NF-κB activity declines rapidly in normal myoblasts, but only slightly in rhabdomyosarcoma cells. However, after treatment of the cells with two different small-molecule NF-κB-inhibiting compounds, the IKK inhibitor curcumin and the proteasome inhibitor lactacystin, we found that neither curcumin nor lactacystin promoted myogenic differentiation in either normal myoblasts or rhabdomyosarcoma cells. Taken together, our data suggest that treatment with curcumin or lactacystin might not be a suitable approach in the treatment of rhabdomyosarcoma.
Authors:
Felicitas Berger; Ingrid Büchsler; Barbara Munz
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-31
Journal Detail:
Title:  Differentiation; research in biological diversity     Volume:  83     ISSN:  1432-0436     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-4-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401650     Medline TA:  Differentiation     Country:  -    
Other Details:
Languages:  ENG     Pagination:  271-281     Citation Subset:  -    
Copyright Information:
Copyright © 2012 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.
Affiliation:
Charité, Institute of Physiology, University Medicine Berlin, Thielallee 71, D-14195 Berlin, Germany.
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