Document Detail


Combination of quercetin and tannic acid in inhibiting 26S proteasome affects S5a and 20S expression and accumulation of ubiquitin resulted in apoptosis in cancer chemoprevention.
MedLine Citation:
PMID:  23241588     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstract To look for oral proteasome inhibitors, the daily food is best source for cancer chemoprevention. A combination of active components from vegetables, coffee, tea, and fruit could be more efficient to inhibit 26S proteasome activities for preventing cancer diseases. Tannic acid and quercetin have been shown to strongly inhibit 26S proteasome activity, but the molecular target involved remains unknown. Overlay assay, peptide assay, western blot, and 2-D gels were used to assess the combination of quercetin and tannic acid as a potential inhibitor. Here, we demonstrated that the combination of quercetin and tannic acid (1) synergistically suppresses chymotrypsin-like, caspase-like, and trypsin-like proteolytic activities, (2) are tightly binding substrates, (3) do not perturb the proteasome structure, (4) inhibit the 26S proteasome affected by ubiquitin, ATP, or β-casein, and (5) inhibit β-casein degradation by the 26S proteasome in vitro. Finally, inhibition of the proteasome by a combination of quercetin plus tannic acid in Hep-2 cells resulted in induction of S5a at low dose, accumulation of ubiquitin, and the cleavage of pro-caspase-3, followed by induction of apoptotic cell death. Evaluating the combination of quercetin and tannic acid as an oral drug to prevent cancer may provide a pharmacological rationale to pursue preclinical trials of this combination.
Authors:
Tsui-Ling Chang; Chi-Hsien Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-5
Journal Detail:
Title:  Biological chemistry     Volume:  -     ISSN:  1437-4315     ISO Abbreviation:  Biol. Chem.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9700112     Medline TA:  Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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