Document Detail

Resveratrol acts as a topoisomerase II poison in human glioma cells.
MedLine Citation:
PMID:  22095529     Owner:  NLM     Status:  MEDLINE    
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.
Stefano Leone; Emiliano Basso; Fabio Polticelli; Renata Cozzi
Related Documents :
22528119 - The polyphenolic ellagitannin vescalagin acts as a preferential catalytic inhibitor of ...
21855309 - Dna in ancient bone - where is it located and how should we extract it?
10564459 - Dna fingerprinting reveals polygyny in the subterranean rodent ctenomys talarum.
21999439 - Evaluation of 8-hydroxy-2'-deoxyguanosine (8-ohdg) adduct levels and dna strand breaks ...
22198329 - Induction of oxidative stress, dna damage and apoptosis in mouse liver after sub-acute ...
10726759 - Low probe concentration can cause problems in multilocus dna fingerprinting (cautionary...
1008819 - The stability, polyadenylic acid content and ribonucleoprotein form of nulcear ribonucl...
355859 - "maturation" of dna duplexes.
6246259 - Baboon endogenous virus genome. i. restriction enzyme map of the unintegrated dna genom...
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.
Department of Biology, University Roma TRE, Rome, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
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
Models, Molecular
Protein Kinases / metabolism
Protein-Serine-Threonine Kinases / metabolism
Stilbenes / pharmacology*
Topoisomerase II Inhibitors / pharmacology*
Tumor Suppressor Proteins / metabolism
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 kinase 2; EC kinase 1; EC Kinases; EC telangiectasia mutated protein; EC Topoisomerases, Type II; EC topoisomerase II alpha; Q369O8926L/resveratrol

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

Previous Document:  Hypothalamic action of glutamate leads to body mass reduction through a mechanism partially dependen...
Next Document:  Baseline characteristics and statistical implications for the OECD 210 fish early life stage chronic...