Document Detail


Cyclooxygenase inhibitors regulate the expression of a TGF-beta superfamily member that has proapoptotic and antitumorigenic activities.
MedLine Citation:
PMID:  11259636     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The antitumorigenic activity of nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase (COX) inhibitors, is well established, but responsible molecular mechanisms are not fully understood. NSAIDs stimulate apoptosis by COX dependent and independent mechanisms in colorectal cells in culture. Identification of genes regulated by COX inhibitors could lead to a better understanding of their proapoptotic and anti-neoplastic activities. Using subtractive hybridization, a cDNA which was designated as NSAID activated gene (NAG-1) was identified from NSAID-treated HCT-116, human colorectal cells. NAG-1 has an identical sequence with a novel member of the TGF-beta superfamily that has 5 different names. In the HCT-116 cells, NAG-1 expression is increased and apoptosis is induced by treatment with some NSAIDs in a concentration and time-dependent manner. NAG-1 transfected cells exhibited increased basal apoptosis, increased response to NSAIDs and reduced soft agar cloning efficiency. Furthermore, transplantable tumors derived from NAG-1 transfected HCT-116 cells showed reduced tumorigenicity in athymic nude mice compared with vector-transfected HCT-116 cells. The increased NAG-1 expression by NSAIDs provides a suitable explanation for COX-independent apoptotic effects of NSAIDs in cultured cells. These data demonstrate that NAG-1 is an antitumorigenic and proapoptotic protein, and its regulation by COX inhibitors may provide new clues for explaining their proapoptotic and antitumorigenic activities.
Authors:
S J Baek; K S Kim; J B Nixon; L C Wilson; T E Eling
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular pharmacology     Volume:  59     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-03-22     Completed Date:  2001-04-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  901-8     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AF173860
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Antineoplastic Agents / metabolism,  pharmacology*
Apoptosis*
Cell Division / drug effects
Colorectal Neoplasms / metabolism*
Cyclooxygenase Inhibitors / pharmacology*
Cytokines / biosynthesis*,  genetics,  pharmacology*
Dose-Response Relationship, Drug
Gene Expression Regulation, Neoplastic / drug effects*
Growth Differentiation Factor 15
Humans
Male
Mice
Mice, Nude
Molecular Sequence Data
RNA, Messenger / metabolism
Transfection
Transforming Growth Factor beta / genetics
Tumor Cells, Cultured
Tumor Stem Cell Assay
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antineoplastic Agents; 0/Cyclooxygenase Inhibitors; 0/Cytokines; 0/GDF15 protein, human; 0/Gdf15 protein, mouse; 0/Growth Differentiation Factor 15; 0/RNA, Messenger; 0/Transforming Growth Factor beta

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


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