Skip to main content

Research Repository

Advanced Search

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.


H. A. Patsos

D. J. Hicks

R. R.H. Dobson

N. Woodman

J. D. Lane

A. C. Williams

C. Paraskeva


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.


Patsos, H. A., Hicks, D. J., Dobson, R. R., Greenhough, A., Woodman, N., Lane, J. D., …Paraskeva, C. (2005). The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: A possible role for cyclooxygenase 2. Gut, 54(12), 1741-1750.

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
Public URL
Publisher URL