Document Detail


GDP366, a novel small molecule dual inhibitor of survivin and Op18, induces cell growth inhibition, cellular senescence and mitotic catastrophe in human cancer cells.
MedLine Citation:
PMID:  20160501     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Accumulating evidence indicates that survivin plays a pivotal role in not only cell survival but also cell cycle progression. Op18/stathmin is an oncoprotein that regulates microtubule stabilization. Both survivin and Op18 have been proposed as therapeutic targets for cancer. However, few small molecule inhibitors of survivin and Op18 have been reported. In this study, we have identified a novel small molecule compound (GDP366) which potently and selectively inhibited the expression of both survivin and Op18. It decreased both the mRNA and protein levels of survivin and Op18. This inhibitory effect was not dependent on the status of p53 and p21 although GDP366 potently increased p53 and p21 levels. GDP366 significantly inhibited the growth of tumor cells in vitro and in vivo (nude mouse model) without rapid induction of apoptosis. GDP366 induced polyploidy in multiple types of cancer cell lines. GDP366 increased chromosomal instability, and induced cellular senescence by inhibiting telomerase activity. We conclude that GDP366 is a novel dual inhibitor of survivin and Op18. Our results warrant further translational evaluation of this compound.
Authors:
Xianping Shi; Deping Wang; Ke Ding; Zhongzheng Lu; Yanli Jin; Jin Zhang; Jingxuan Pan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-20
Journal Detail:
Title:  Cancer biology & therapy     Volume:  9     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-08-19     Completed Date:  2011-01-06     Revised Date:  2013-02-05    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  640-50     Citation Subset:  IM    
Affiliation:
Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Bicyclo Compounds, Heterocyclic / pharmacology*
Cell Aging / drug effects
Colorectal Neoplasms / drug therapy*,  pathology
HCT116 Cells
HeLa Cells
Humans
Inhibitor of Apoptosis Proteins
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Microtubule-Associated Proteins / antagonists & inhibitors*
Phenylurea Compounds / pharmacology*
Stathmin / antagonists & inhibitors*
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/BIRC5 protein, human; 0/Bicyclo Compounds, Heterocyclic; 0/GDP 366; 0/Inhibitor of Apoptosis Proteins; 0/Microtubule-Associated Proteins; 0/Phenylurea Compounds; 0/Stathmin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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