| Anticancer effects of the p53 activator nutlin-3 in Ewing's sarcoma cells. | |
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MedLine Citation:
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PMID: 21334198 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Mutation of p53 is rare in Ewing's sarcoma (ES), suggesting that targeting and activation of wild-type p53 may be an effective therapeutic strategy for ES. The recently developed small-molecule MDM2 inhibitor nutlin-3 restores wild-type p53 function, resulting in the inhibition of cancer cell growth and the induction of apoptosis. In the present study, we explored the responsiveness of ES cell lines with wild-type or mutated p53 to nutlin-3. We found that treatment with nutlin-3 increased p53 level and induced p53 target gene expression (MDM2, p21, PUMA) in ES cells with wild-type p53, but not in ES cells with mutated p53. Consistently, nutlin-3 elicited apoptosis only in wild-type p53 cells, as assessed by caspase-3 activity assay and flow cytometric analyses of mitochondrial depolarisation and DNA fragmentation. In addition, we found nutlin-3 to evoke cellular senescence, indicating that nutlin-3 induces pleiotropic anticancer effects in ES. Furthermore, combined treatment with nutlin-3 and an inhibitor of NF-κB produced synergistic antineoplastic activity in ES cells. Our findings suggest that the direct activation of p53 by nutlin-3 treatment may be a useful new therapeutic approach for patients with ES. |
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Authors:
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Jürgen Sonnemann; Chithra D Palani; Susan Wittig; Sabine Becker; Friederike Eichhorn; Astrid Voigt; James F Beck |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-17 |
Journal Detail:
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Title: European journal of cancer (Oxford, England : 1990) Volume: - ISSN: 1879-0852 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9005373 Medline TA: Eur J Cancer Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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University Children's Hospital Jena, Department of Paediatric Haematology and Oncology, Jena, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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