Source:http://linkedlifedata.com/resource/pubmed/id/20802516
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
47
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| pubmed:dateCreated |
2010-11-25
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| pubmed:abstractText |
New anti-telomere strategies represent important goals for the development of selective cancer therapies. In this study, we reported that uncapped telomeres, resulting from pharmacological stabilization of quadruplex DNA by RHPS4 (3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate), trigger specific recruitment and activation of poly-adenosine diphosphate (ADP) ribose polymerase I (PARP1) at the telomeres, forming several ADP-ribose polymers that co-localize with the telomeric repeat binding factor 1 protein and are inhibited by selective PARP(s) inhibitors or PARP1-specific small interfering RNAs. The knockdown of PARP1 prevents repairing of RHPS4-induced telomere DNA breaks, leading to increases in chromosome abnormalities and eventually to the inhibition of tumor cell growth both in vitro and in xenografts. More interestingly, the integration of a TOPO1 inhibitor on the combination treatment proved to have a high therapeutic efficacy ensuing a complete regression of the tumor as well as a significant increase in overall survival and cure of mice even when treatments started at a very late stage of tumor growth. Overall, this work reveals the unexplored link between the PARP1 and G-quadruplex ligands and demonstrates the excellent efficacy of a multi-component strategy based on the use of PARP inhibitors in telomere-based therapy.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3,11-difluoro-6,8,13-trimethyl-8H-qu...,
http://linkedlifedata.com/resource/pubmed/chemical/Acridines,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
|
| pubmed:issn |
1476-5594
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| pubmed:author |
pubmed-author:BiroccioAA,
pubmed-author:D'IncalciMM,
pubmed-author:GilsonEE,
pubmed-author:GrazianiGG,
pubmed-author:IachettiniSS,
pubmed-author:LeonettiCC,
pubmed-author:OrlandiAA,
pubmed-author:PasseraLL,
pubmed-author:PopovA BAB,
pubmed-author:RizzoAA,
pubmed-author:SalvatiEE,
pubmed-author:ScarsellaMM,
pubmed-author:StevensM F GMF,
pubmed-author:TentoriLL,
pubmed-author:ZupiGG
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
25
|
| pubmed:volume |
29
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
6280-93
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| pubmed:meshHeading |
pubmed-meshheading:20802516-Acridines,
pubmed-meshheading:20802516-Animals,
pubmed-meshheading:20802516-Antineoplastic Agents,
pubmed-meshheading:20802516-DNA Damage,
pubmed-meshheading:20802516-DNA Repair,
pubmed-meshheading:20802516-Drug Synergism,
pubmed-meshheading:20802516-Enzyme Activation,
pubmed-meshheading:20802516-Enzyme Inhibitors,
pubmed-meshheading:20802516-G-Quadruplexes,
pubmed-meshheading:20802516-HCT116 Cells,
pubmed-meshheading:20802516-HT29 Cells,
pubmed-meshheading:20802516-Humans,
pubmed-meshheading:20802516-Male,
pubmed-meshheading:20802516-Mice,
pubmed-meshheading:20802516-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:20802516-Protein Transport,
pubmed-meshheading:20802516-Telomere,
pubmed-meshheading:20802516-Xenograft Model Antitumor Assays
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| pubmed:year |
2010
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| pubmed:articleTitle |
PARP1 is activated at telomeres upon G4 stabilization: possible target for telomere-based therapy.
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| pubmed:affiliation |
Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|