Document Detail


Antitumor effect of novel small chemical inhibitors of Snail-p53 binding in K-Ras-mutated cancer cells.
MedLine Citation:
PMID:  20531295     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
p53 is frequently mutated by genetic alternation or suppressed by various kinds of cellular signaling pathways in human cancers. Recently, we have revealed that p53 is suppressed and eliminated from cells by direct binding with oncogenic K-Ras-induced Snail. On the basis of the fact, we generated specific inhibitors against p53-Snail binding (GN25 and GN29). These chemicals can induce p53 expression and functions in K-Ras-mutated cells. However, it does not show cytotoxic effect on normal cells or K-Ras-wild-type cells. Moreover, GN25 can selectively activate wild-type p53 in p53(WT/MT) cancer cells. But single allelic mt p53 containing cell line, Panc-1, does not respond to our chemical. In vivo xenograft test also supports the antitumor effect of GN25 in K-Ras-mutated cell lines. These results suggest that our compounds are strong candidate for anticancer drug against K-Ras-initiated human cancers including pancreatic and lung cancers.
Authors:
S-H Lee; G-N Shen; Y S Jung; S-J Lee; J-Y Chung; H-S Kim; Y Xu; Y Choi; J-W Lee; N-C Ha; G Y Song; B-J Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-07
Journal Detail:
Title:  Oncogene     Volume:  29     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-12     Completed Date:  2010-09-03     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  4576-87     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / chemistry*,  pharmacology*
Cell Line, Tumor
Cell Transformation, Neoplastic
Child
Drug Evaluation, Preclinical
Female
Genes, ras / genetics*
Humans
Mice
Mutation
Naphthoquinones / chemistry*,  pharmacology*
Neoplasms / drug therapy*,  genetics,  pathology*
Protein Binding / drug effects
Small Molecule Libraries / chemistry,  pharmacology
Transcription Factors / metabolism*
Tumor Suppressor Protein p53 / metabolism*
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/GN25 compound; 0/Naphthoquinones; 0/Small Molecule Libraries; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 0/snail family transcription factors

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


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