Document Detail

NSAID inhibition of prostate cancer cell migration is mediated by Nag-1 Induction via the p38 MAPK-p75(NTR) pathway.
MedLine Citation:
PMID:  21097678     Owner:  NLM     Status:  MEDLINE    
The nonsteroidal anti-inflammatory drugs (NSAID) R-flurbiprofen and ibuprofen have been shown to induce expression of p75(NTR) (neurotrophin receptor) in prostate cancer cell lines. p75(NTR), a tumor necrosis factor receptor superfamily member, is a proapoptotic protein that functions as a tumor suppressor in the human prostate. Expression of p75(NTR) is lost as prostate cancer progresses and is minimal in several metastatic prostate cancer cell lines. NSAIDs induce p75(NTR) through activation of the p38 mitogen-activated protein kinase (MAPK) pathway, with a concomitant decrease in cell survival. Here, we show that treatment with R-flurbiprofen and ibuprofen induces expression of the NSAID-activated gene-1 (Nag-1) protein, a divergent member of the TGF beta (TGF-β) family, in PC-3 cells. Using the selective pharmacologic inhibitor of p38 MAPK, SB202190, and p38 MAPK-specific siRNA (small interfering RNA), we show that Nag-1 induction following NSAID treatment is mediated by the p38 MAPK pathway. p75(NTR)-specific siRNA pretreatment shows that Nag-1 induction by NSAIDs is downstream of p75(NTR) induction. Decreased survival of NSAID-treated cells is rescued by p75(NTR)-specific siRNA but not by Nag-1 siRNA. Transwell chamber and in vitro wound healing assays demonstrate decreased cell migration upon NSAID treatment. Pretreatment of PC-3 cells with p75(NTR) and Nag-1-specific siRNA shows that NSAID inhibition of cell migration is mediated by Nag-1 and p75(NTR). These results demonstrate a role for Nag-1 in NSAID inhibition of cell migration, but not survival.
Shehla Wynne; Daniel Djakiew
Related Documents :
22656888 - Nitric oxide affects immune cells bioenergetics: long-term effects of nitric-oxide deri...
22672708 - Cell division and density of symbiotic chlorella variabilis of the ciliate paramecium b...
21190228 - Inhibition of acid ceramidase by a 2-substituted aminoethanol amide synergistically sen...
15913418 - Cytologic features of high-grade squamous intraepithelial lesion in conventional slides...
8371098 - Giant and binucleate trophoblast cells of mammals.
192738 - The relative amounts of the cytoplasmic rna species in normal, transformed and senescen...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-11-19
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  8     ISSN:  1557-3125     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-17     Completed Date:  2011-03-10     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1656-64     Citation Subset:  IM    
Copyright Information:
©2010 AACR.
Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, 3900 Reservoir Road NW, Washington, DC 20057, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Cell Line, Tumor
Cell Movement / drug effects*
Flurbiprofen / pharmacology,  therapeutic use
Growth Differentiation Factor 15 / genetics*,  metabolism
Ibuprofen / pharmacology
Imidazoles / pharmacology
MAP Kinase Signaling System
Nerve Tissue Proteins / genetics,  metabolism*
Prostatic Neoplasms / drug therapy*,  metabolism*,  pathology
Pyridines / pharmacology
RNA, Small Interfering / genetics
Receptors, Nerve Growth Factor / genetics,  metabolism*
Transforming Growth Factor beta1 / metabolism
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors,  genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/GDF15 protein, human; 0/Growth Differentiation Factor 15; 0/Imidazoles; 0/NGFR protein, human; 0/Nerve Tissue Proteins; 0/Pyridines; 0/RNA, Small Interfering; 0/Receptors, Nerve Growth Factor; 0/Transforming Growth Factor beta1; 15687-27-1/Ibuprofen; 5104-49-4/Flurbiprofen; EC Mitogen-Activated Protein Kinases

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

Previous Document:  Commutability limitations influence quality control results with different reagent lots.
Next Document:  Quality and production trait genetics of farmed European whitefish Coregonus lavaretus.