| Resveratrol induces senescence-like growth inhibition of U-2 OS cells associated with the instability of telomeric DNA and upregulation of BRCA1. | |
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MedLine Citation:
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PMID: 19559722 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Resveratrol decreases cancer risk and improves health of laboratory animals. However, it can also promote genomic instability. Part of the beneficial activity of resveratrol may result from the activation of SIRT1 deacetylase. We examined how resveratrol influenced the growth of human cancer cell lines of different origin: osteosarcoma (U-2 OS) and lung adenocarcinoma (A549) and how it modulated the expression as well as the localization of key proteins, involved in DNA repair and cell cycle regulation. Resveratrol-induced growth arrest was associated with signs of stress-induced senescence. Differential expression of BRCA1, cyclin B1, pRb and p21 in U-2 OS and A549 cells indicates that resveratrol can engage various molecular mechanisms to arrest cell cycle progression. In subset of U-2 OS cells, the upregulated BRCA1 formed foci closely associated with WRN and the telomeric protein (TRF1). Moreover, resveratrol induced telomeric instability in U-2 OS cells and the activation of DNA damage signaling in both cell lines, manifested as the phosphorylation of histone H2AX at serine 139 and of p53 at serines 15 and 37. Our data are consistent with the hypothesis that resveratrol inhibits cell growth and induces senescence by altering DNA metabolism. |
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Authors:
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Marek Rusin; Artur Zajkowicz; Dorota Butkiewicz |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-25 |
Journal Detail:
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Title: Mechanisms of ageing and development Volume: 130 ISSN: 1872-6216 ISO Abbreviation: Mech. Ageing Dev. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-07-27 Completed Date: 2009-09-28 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0347227 Medline TA: Mech Ageing Dev Country: Ireland |
Other Details:
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Languages: eng Pagination: 528-37 Citation Subset: IM |
Affiliation:
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Department of Tumor Biology, Maria Skłodowska - Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland. rusinm@rocketmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antioxidants
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pharmacology* BRCA1 Protein / biosynthesis* Blotting, Southern Cell Aging Cell Line, Tumor DNA / metabolism* Gene Expression Regulation, Neoplastic* Humans In Situ Hybridization, Fluorescence Models, Biological Serine / chemistry Sirtuin 1 Sirtuins / metabolism Stilbenes / pharmacology* Telomere / metabolism, ultrastructure* Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/BRCA1 Protein; 0/BRCA1 protein, human; 0/Stilbenes; 501-36-0/resveratrol; 56-45-1/Serine; 9007-49-2/DNA; EC 3.5.1.-/SIRT1 protein, human; EC 3.5.1.-/Sirtuin 1; EC 3.5.1.-/Sirtuins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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