Document Detail


Carrageenan induces cell cycle arrest in human intestinal epithelial cells in vitro.
MedLine Citation:
PMID:  18287351     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multiple studies in animal models have shown that the commonly used food additive carrageenan (CGN) induces inflammation and intestinal neoplasia. We performed the first studies to determine the effects of CGN exposure on human intestinal epithelial cells (IEC) in tissue culture and tested the effect of very low concentrations (1-10 mg/L) of undegraded, high-molecular weight CGN. These concentrations of CGN are less than the anticipated exposure of the human colon to CGN from the average Western diet. In the human colonic epithelial cell line NCM460 and in primary human colonic epithelial cells that were exposed to CGN for 1-8 d, we found increased cell death, reduced cell proliferation, and cell cycle arrest compared with unexposed control cells. After 6-8 d of CGN exposure, the percentage of cells reentering G0-G1 significantly decreased and the percentages of cells in S and G2-M phases significantly increased. Increases in activated p53, p21, and p15 followed CGN exposure, consistent with CGN-induced cell cycle arrest. Additional data, including DNA ladder, poly ADP ribose polymerase Western blot, nuclear DNA staining, and activities of caspases 3 and 7, indicated no evidence of increased apoptosis following CGN exposure and were consistent with CGN-induced necrotic cell death. These data document for the first time, to our knowledge, marked adverse effects of low concentrations of CGN on survival of normal human IEC and suggest that CGN exposure may have a role in development of human intestinal pathology.
Authors:
Sumit Bhattacharyya; Alip Borthakur; Pradeep K Dudeja; Joanne K Tobacman
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of nutrition     Volume:  138     ISSN:  1541-6100     ISO Abbreviation:  J. Nutr.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-21     Completed Date:  2008-03-21     Revised Date:  2011-05-04    
Medline Journal Info:
Nlm Unique ID:  0404243     Medline TA:  J Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  469-75     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Illinois at Chicago and Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Carrageenan / pharmacology*
Caspase 3 / genetics,  metabolism
Caspase 7 / genetics,  metabolism
Cell Cycle / drug effects*
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Collagen Type XI / genetics,  metabolism
Cyclin-Dependent Kinase Inhibitor p15 / genetics,  metabolism
Cyclin-Dependent Kinase Inhibitor p21 / genetics,  metabolism
Epithelial Cells / cytology*,  drug effects*,  metabolism
Gene Expression Regulation
Humans
Intestinal Mucosa / cytology*
Kruppel-Like Transcription Factors / genetics,  metabolism
Necrosis
Nuclear Proteins / genetics,  metabolism
Oligonucleotide Array Sequence Analysis
Time Factors
Trans-Activators / genetics,  metabolism
Tumor Suppressor Protein p53 / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
DK54016/DK/NIDDK NIH HHS; DK68324/DK/NIDDK NIH HHS; P01 DK067887-01A10001/DK/NIDDK NIH HHS; R01 DK054016-10/DK/NIDDK NIH HHS; R01 DK068324-03/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/CDKN2B protein, human; 0/COL11A2 protein, human; 0/Collagen Type XI; 0/Cyclin-Dependent Kinase Inhibitor p15; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/GKLF protein; 0/JMY protein, human; 0/Kruppel-Like Transcription Factors; 0/Nuclear Proteins; 0/Trans-Activators; 0/Tumor Suppressor Protein p53; 9000-07-1/Carrageenan; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7

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


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