| The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: a possible role for cyclooxygenase 2. | |
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MedLine Citation:
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PMID: 16099783 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-08-11 |
Journal Detail:
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Title: Gut Volume: 54 ISSN: 0017-5749 ISO Abbreviation: Gut Publication Date: 2005 Dec |
Date Detail:
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Created Date: 2005-11-14 Completed Date: 2005-12-12 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 2985108R Medline TA: Gut Country: England |
Other Details:
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Languages: eng Pagination: 1741-50 Citation Subset: AIM; IM |
Affiliation:
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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. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amidohydrolases
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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 Humans Polyunsaturated Alkamides Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 0/Cyclooxygenase Inhibitors; 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 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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