H. A. Patsos
The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: A possible role for cyclooxygenase 2
Patsos, H. A.; Hicks, D. J.; Dobson, R. R.H.; Greenhough, A.; Woodman, N.; Lane, J. D.; Williams, A. C.; Paraskeva, C.
Authors
D. J. Hicks
R. R.H. Dobson
Alexander Greenhough Alexander.Greenhough@uwe.ac.uk
Associate Professor of Health Diagnostics
N. Woodman
J. D. Lane
A. C. Williams
C. Paraskeva
Abstract
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.
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 5, 2005 |
Online Publication Date | Aug 11, 2005 |
Publication Date | Dec 1, 2005 |
Journal | Gut |
Print ISSN | 0017-5749 |
Publisher | BMJ Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 54 |
Issue | 12 |
Pages | 1741-1750 |
DOI | https://doi.org/10.1136/gut.2005.073403 |
Public URL | https://uwe-repository.worktribe.com/output/1055735 |
Publisher URL | http://dx.doi.org/10.1136/gut.2005.073403 |
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