The numbers of cancer patients and deaths by colorectal cancer (CRC) in Japan are increasing every year. Cyclooxgenase-2 (COX-2) is an enzyme and biomarker of CRC that produces prostaglandins (PG) from arachidonic acid and plays important roles in the inflammation. We have been reported that COX-2 expression is induced by PGE­₂ stimulation in HCA-7, a human early colon cancer cells.
2-arachidonoylglycerol (2-AG) is an endocannabinoid that has been reported to exhibit anticancer effects against various cancers. However, the detailed mechanisms of anticancer effects of 2-AG have not been clarified. Therefore, the purpose of this study is to elucidate the effects of 2-AG on HCA-7 cells and their mechanisms.
As the results, COX-2 expression induced by PGE₂ was significantly and concentration-dependently inhibited by pretreatment with 2-AG in HCA-7 cells. This effect was not observed with anandamide, a similar endocannabinoid as 2-AG, or their metabolites. Interestingly, 2-AG did not affect the transcriptional activity of COX-2, whereas RT-PCR showed that COX-2 mRNA expression was suppressed by 2-AG.
These results suggest that 2-AG but not anandamide, suppresses COX-2 expression induced by PGE_{2 ­}in HCA-7 cells, and that this effect of 2-AG may not be due to transcriptional inhibition, but rather to decrease of mRNA stability.