Document Detail


Escherichia coli verotoxin 1 mediates apoptosis in human HCT116 colon cancer cells by inducing overexpression of the GADD family of genes and S phase arrest.
MedLine Citation:
PMID:  16297916     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Escherichia coli verotoxin 1 (VT1) inhibits protein synthesis, cell proliferation, and damages endothelial cell in the hemolytic uremic syndrome. VT1 can specifically bind and act on endothelial cells as well as on many tumor cells because these cells express its high affinity receptor, globotriaosylceramide. This indicates that VT1 may have both antiangiogenic and antineoplastic activities. We investigated this potential of VT1 by incubating several colon cancer cell lines with VT1 for different time periods and found that HCT116 cells were especially sensitive to VT1. A combination of morphological studies, flow cytometry, DNA laddering and annexin V staining confirmed that VT1 irreversibly arrests these cells in S phase within 24 h and prolonged incubation triggers DNA fragmentation. Concomitant to the activation of the S phase checkpoint, increased levels of mRNA and proteins of growth arrest and DNA damage-inducible gene family that include GADD34, GADD45alpha, and GADD45beta was observed. Interestingly, no significant changes in expression of key cell cycle related proteins such as cdk2, cdk4, p21, p27, and p53 was found during the S phase arrest and apoptosis. We therefore suggest that GADD proteins might play an important role in VT1 induced S phase arrest and programmed cell death in HCT116 cells.
Authors:
Rabindra N Bhattacharjee; Kwon-Sam Park; Satoshi Uematsu; Kazuhisa Okada; Katsuaki Hoshino; Kiyoshi Takeda; Osamu Takeuchi; Shizuo Akira; Tetsuya Iida; Takeshi Honda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-11-09
Journal Detail:
Title:  FEBS letters     Volume:  579     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-28     Completed Date:  2006-01-19     Revised Date:  2011-04-12    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  6604-10     Citation Subset:  IM    
Affiliation:
Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Differentiation / genetics*
Apoptosis / drug effects*
Cell Cycle Proteins / genetics
Cell Line, Tumor
Colonic Neoplasms / pathology*
Escherichia coli Proteins / pharmacology
Gene Expression Regulation / drug effects*
Humans
Nuclear Proteins / genetics
S Phase*
Shiga Toxin 1 / pharmacology*
Chemical
Reg. No./Substance:
0/Antigens, Differentiation; 0/Cell Cycle Proteins; 0/Escherichia coli Proteins; 0/GADD45A protein, human; 0/GADD45B protein, human; 0/Nuclear Proteins; 0/Shiga Toxin 1; EC 3.1.3.16/PPP1R15A protein, human

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