The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: a possible role for cyclooxygenase 2. Issue 12 (11th August 2005)

• Record Type: Journal Article
• Authors: Patsos, H A; Hicks, D J; Dobson, R R H; Greenhough, A; Woodman, N; Lane, J D; Williams, A C; Paraskeva, C
• Is Part Of: Gut. Volume 54:Issue 12(2005)
• Page Start: 1741
• Page End: 1750
• Publication Date: 2005-08-11
• Subjects: Δ9-THC, Δ9-tetrahydrocannabinol -- AEA, arachidonoyl ethanolamine (anandamide) -- CB, cannabinoid -- COX, cyclooxygenase -- CRC, colorectal carcinoma -- FAAH, fatty acid amide hydrolase -- FBS, fetal bovine serum -- HRP, horseradish peroxidase -- PG, prostaglandin -- PG-EA, prostaglandin-ethanolamide -- PI, propidium iodide -- RT-PCR, reverse transcriptase-polymerase chain reaction; cannabinoid -- anandamide -- colorectal carcinoma -- cyclooxygenase-2 -- fatty acid amide hydrolase -- cell death; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2005.073403
• Languages: English
• ISSNs: 0017-5749

Abstract

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.