Document Detail


Resveratrol acts as a topoisomerase II poison in human glioma cells.
MedLine Citation:
PMID:  22095529     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently, we demonstrated that Resveratrol (RSV), a well known natural stilbene, is able to induce a delay in S progression with a concomitant increase in γH2AX expression in U87 glioma cells. Furthermore, we showed that it inhibits the ability of recombinant human topoisomerase IIα to decatenate kDNA in vitro. Because proliferating tumor cells express topoisomerases at high levels and these enzymes are important targets of some of the most successful anticancer drugs, we tested whether RSV is able to poison topoisomerase IIα in glioma cells. Then, we monitored the increase of micronuclei in RSV treated U87 cells as a consequence of the conversion of TOPOII/DNA cleavable complexes to permanent DNA damage. Finally, we assayed the ability of RSV in modulating the expression of target proteins involved in DNA damage signalling, namely ATR, ATM, Chk1, Chk2 and γH2AX. Through a molecular modelling here we show that RSV binds at the TOPOII/DNA interface thus establishing several hydrogen bonds. Moreover, we show that RSV poisons TOPOIIα so inducing DNA damage; ATM, Chk2 and γH2AX are involved in the DNA damage signalling after RSV treatment.
Authors:
Stefano Leone; Emiliano Basso; Fabio Polticelli; Renata Cozzi
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Publication Detail:
Type:  Journal Article     Date:  2012-01-03
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  131     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-05-28     Completed Date:  2012-07-30     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E173-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 UICC.
Affiliation:
Department of Biology, University Roma TRE, Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Neoplasm / metabolism
Cell Cycle Checkpoints / drug effects
Cell Cycle Proteins / metabolism
Cell Line, Tumor
DNA Damage*
DNA Topoisomerases, Type II / metabolism
DNA-Binding Proteins / metabolism
Glioma / drug therapy,  pathology*
Histones / metabolism
Humans
Models, Molecular
Protein Kinases / metabolism
Protein-Serine-Threonine Kinases / metabolism
Stilbenes / pharmacology*
Topoisomerase II Inhibitors / pharmacology*
Tumor Suppressor Proteins / metabolism
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/H2AFX protein, human; 0/Histones; 0/Stilbenes; 0/Topoisomerase II Inhibitors; 0/Tumor Suppressor Proteins; EC 2.7.-/Protein Kinases; EC 2.7.1.-/ATR protein, human; EC 2.7.1.11/checkpoint kinase 2; EC 2.7.11.1/Checkpoint kinase 1; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/ataxia telangiectasia mutated protein; EC 5.99.1.3/DNA Topoisomerases, Type II; EC 5.99.1.3/DNA topoisomerase II alpha; Q369O8926L/resveratrol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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