Document Detail


Induction of apoptosis on K562 cell line and double strand breaks on colon cancer cell line expressing high affinity receptor for granulocyte macrophage-colony stimulating factor (GM-CSF).
MedLine Citation:
PMID:  18392089     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Immunotoxins are comprised of both the cell targeting and the cell killing moieties. We previously established a new immunotoxin, i.e. Shiga toxin granulocyte macrophage-colony stimulating factor (StxA1-GM-CSF), comprises of catalytic domain of Stx, as a killing moiety and GM-CSF, as a cell targeting moiety. In this study, the ability of the immunotoxin to induce apoptosis and double strand breaks (DSB) on different cell lines was investigated. METHODS: The recombinant hybrid protein was expressed in bacterial expression system and purified with nickel-nitrilotriacetate acid resin. The K562 (erythroid leukemia) cell line and LS174 (colon carcinoma) were used in this study. The neutral comet assay was carried out for the detection of DSB and Hoechst staining was performed for apoptosis. RESULTS: StxA1-GM-CSF effectively induced apoptosis on K562 cell line and DNA Double Strand Break (DSB) were observed on colon cancer cell line treated with StxA1-GM-CSF. CONCLUSION: This novel action i.e. DNA damage might be a relevant mechanism of action for StxA1-GM-CSF that is designed to act as immunotoxin, although further investigation is required.
Authors:
Mehryar Habibi Roudkenar; Saeid Bouzari; Yoshikazu Kuwahara; Amaneh Mohammadi Roushandeh; Taisuke Baba; Mana Oloomi; Manabu Fukumoto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Iranian biomedical journal     Volume:  12     ISSN:  1028-852X     ISO Abbreviation:  Iran. Biomed. J.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-04-08     Completed Date:  2008-05-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9814853     Medline TA:  Iran Biomed J     Country:  Iran    
Other Details:
Languages:  eng     Pagination:  1-6     Citation Subset:  IM    
Affiliation:
Research Center, Iranian Blood Transfusion Organization, Tehran, Iran.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects*
Colonic Neoplasms / chemistry,  drug therapy*
DNA Breaks, Double-Stranded / drug effects*
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
Histones / analysis
Humans
Immunotoxins / pharmacology*
K562 Cells
Protein Subunits / pharmacology*
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / analysis*
Shiga Toxin / pharmacology*
Chemical
Reg. No./Substance:
0/H2AFX protein, human; 0/Histones; 0/Immunotoxins; 0/Protein Subunits; 0/Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; 0/Shiga toxin subunit A; 75757-64-1/Shiga Toxin; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor

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