| Resveratrol acts as a topoisomerase II poison in human glioma cells. | |
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MedLine Citation:
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PMID: 22095529 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 it inhibits the ability of recombinant human Topoisomerase IIα to decatenate kDNA in vitro. Because proliferating tumour 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 resveratrol poisons TOPOIIα so inducing DNA damage; ATM, Chk2 and γH2AX are involved in the DNA damage signalling after RSV treatment. |
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Authors:
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Stefano Leone; Emiliano Basso; Fabio Polticelli; Renata Cozzi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-18 |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: - ISSN: 1097-0215 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 UICC. |
Affiliation:
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Department of Biology, University "Roma TRE", Rome, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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