Document Detail


Effects of thymoquinone on isolated and cellular proteasomes.
MedLine Citation:
PMID:  20412058     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Thymoquinone, a naturally derived agent, has been shown to possess antioxidant, antiproliferative and proapoptotic activities. In the present study, we explored thymoquinone effects on the proteasomal complex, the major system involved in the removal of damaged, oxidized and misfolded proteins. In purified 20S complexes, subunit-dependent and composition-dependent inhibition was observed, and the chymotrypsin-like and trypsin-like activities were the most susceptible to thymoquinone treatment. U87 MG and T98G malignant glioma cells were treated with thymoquinone, and 20S and 26S proteasome activity was measured. Inhibition of the complex was evident in both cell lines, but predominantly in U87 MG cells, and was accompanied by accumulation of ubiquitin conjugates. Accumulation of p53 and Bax, two proteasome substrates with proapoptotic activity, was observed in both cell lines. Our results demonstrate that thymoquinone induces selective and time-dependent proteasome inhibition, both in isolated enzymes and in glioblastoma cells, and suggest that this mechanism could be implicated in the induction of apoptosis in cancer cells.
Authors:
Valentina Cecarini; Luana Quassinti; Alessia Di Blasio; Laura Bonfili; Massimo Bramucci; Giulio Lupidi; Massimiliano Cuccioloni; Matteo Mozzicafreddo; Mauro Angeletti; Anna Maria Eleuteri
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The FEBS journal     Volume:  277     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-23     Completed Date:  2010-05-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2128-41     Citation Subset:  IM    
Affiliation:
University of Camerino, Italy. valentina.cecarini@unicam.it <valentina.cecarini@unicam.it>
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MeSH Terms
Descriptor/Qualifier:
Benzoquinones / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Glioblastoma / metabolism,  pathology
Humans
Molecular Structure
Protease Inhibitors / pharmacology*
Proteasome Endopeptidase Complex / antagonists & inhibitors*,  isolation & purification,  metabolism
Tumor Suppressor Protein p53 / metabolism
bcl-2-Associated X Protein / metabolism
Chemical
Reg. No./Substance:
0/BAX protein, human; 0/Benzoquinones; 0/Protease Inhibitors; 0/TP53 protein, human; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 490-91-5/thymoquinone; EC 3.4.25.1/Proteasome Endopeptidase Complex

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