| MDM2 inhibitor Nutlin-3a suppresses proliferation and promotes apoptosis in osteosarcoma cells. | |
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MedLine Citation:
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PMID: 22843172 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Restoring p53 activity by inhibiting the interaction between p53 and the mouse double minutes clone 2 (MDM2) offers an attractive approach to cancer therapy. Nutlin-3a is a small-molecule inhibitor that inhibits MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. In this study, we determined the efficacy of Nutlin-3a in inducing p53-mediated cell death in osteosarcoma (OS) cell lines both in vivo and in vitro. Targeted disruption of the p53-MDM2 interaction by Nutlin-3a stabilizes p53 and selectively activates the p53 pathway only in OS cells with wild-type p53, resulting in a pronounced anti-proliferative and cytotoxic effect due to G1 cell cycle arrest and apoptosis both in vitro and in vivo. p53 dependence of these alternative outcomes of Nutlin-3a treatment was shown by the abrogation of these effects when p53 was knocked-down by small interfering RNA. These data suggest that the disruption of p53-MDM2 interaction by Nutlin-3a might be beneficial for OS patients with MDM2 amplification and wt p53 status. |
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Authors:
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Bo Wang; Liming Fang; Hui Zhao; Tong Xiang; Dechun Wang |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Acta biochimica et biophysica Sinica Volume: 44 ISSN: 1745-7270 ISO Abbreviation: Acta Biochim. Biophys. Sin. (Shanghai) Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101206716 Medline TA: Acta Biochim Biophys Sin (Shanghai) Country: China |
Other Details:
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Languages: eng Pagination: 685-91 Citation Subset: IM |
Affiliation:
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Department of Orthopedics, the Second Hospital of Beijing Corps of Chinese People's Armed Police Force, Beijing 100073, China. |
Export Citation:
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Descriptor/Qualifier:
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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