Document Detail


The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: a possible role for cyclooxygenase 2.
MedLine Citation:
PMID:  16099783     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND AIMS: Cyclooxygenase 2 (COX-2) is upregulated in most colorectal cancers and is responsible for metabolism of the endogenous cannabinoid, anandamide, into prostaglandin-ethanolamides (PG-EAs). The aims of this study were to determine whether anandamide and PG-EAs induce cell death in colorectal carcinoma (CRC) cells, and whether high levels of COX-2 in CRC cells could be utilised for their specific targeting for cell death by anandamide.
METHODS: We determined the effect of anandamide on human CRC cell growth by measuring cell growth and cell death, whether this was dependent on COX-2 protein expression or enzyme activity, and the potential involvement of PG-EAs in induction of cell death.
RESULTS: Anandamide inhibited the growth of CRC cell lines HT29 and HCA7/C29 (moderate and high COX-2 expressors, respectively) but had little effect on the very low COX-2 expressing CRC cell line, SW480. Induction of cell death in HT29 and HCA7/C29 cell lines was partially rescued by the COX-2 selective inhibitor NS398. Cell death induced by anandamide was neither apoptosis nor necrosis. Furthermore, inhibition of fatty acid amide hydrolase potentiated the non-apoptotic cell death, indicating that anandamide induced cell death was mediated via metabolism of anandamide by COX-2, rather than its degradation into arachidonic acid and ethanolamine. Interestingly, both PGE2-EA and PGD2-EA induced classical apoptosis.
CONCLUSIONS: These findings suggest anandamide may be a useful chemopreventive/therapeutic agent for colorectal cancer as it targets cells that are high expressors of COX-2, and may also be used in the eradication of tumour cells that have become resistant to apoptosis.
Authors:
H A Patsos; D J Hicks; R R H Dobson; A Greenhough; N Woodman; J D Lane; A C Williams; C Paraskeva
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-08-11
Journal Detail:
Title:  Gut     Volume:  54     ISSN:  0017-5749     ISO Abbreviation:  Gut     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-14     Completed Date:  2005-12-12     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  England    
Other Details:
Languages:  eng     Pagination:  1741-50     Citation Subset:  AIM; IM    
Affiliation:
Cancer Research UK Colorectal Tumour Biology Group, Department of Pathology and Microbiology, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, UK.
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MeSH Terms
Descriptor/Qualifier:
Amidohydrolases / antagonists & inhibitors
Apoptosis / drug effects
Arachidonic Acids / antagonists & inhibitors,  pharmacology*
Cell Death / drug effects
Colorectal Neoplasms / enzymology,  metabolism,  pathology*
Cyclooxygenase 2 / physiology*
Cyclooxygenase Inhibitors / pharmacology
Dinoprostone / analogs & derivatives,  biosynthesis
Dose-Response Relationship, Drug
Endocannabinoids
Humans
Polyunsaturated Alkamides
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Cyclooxygenase Inhibitors; 0/Endocannabinoids; 0/Polyunsaturated Alkamides; 0/prostaglandin E2 ethanolamide; 363-24-6/Dinoprostone; 94421-68-8/anandamide; EC 1.14.99.1/Cyclooxygenase 2; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase
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