Document Detail


MDM2 inhibitor Nutlin-3a suppresses proliferation and promotes apoptosis in osteosarcoma cells.
MedLine Citation:
PMID:  22843172     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Bo Wang; Liming Fang; Hui Zhao; Tong Xiang; Dechun Wang
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Acta biochimica et biophysica Sinica     Volume:  44     ISSN:  1745-7270     ISO Abbreviation:  Acta Biochim. Biophys. Sin. (Shanghai)     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101206716     Medline TA:  Acta Biochim Biophys Sin (Shanghai)     Country:  China    
Other Details:
Languages:  eng     Pagination:  685-91     Citation Subset:  IM    
Affiliation:
Department of Orthopedics, the Second Hospital of Beijing Corps of Chinese People's Armed Police Force, Beijing 100073, China.
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