Clinical-alimentary tractPossible endocannabinoid control of colorectal cancer growth☆
Section snippets
Drugs
AEA and 2-AG were purchased from Cayman Chemicals, and ACEA, Met-Fluoro-anandamide, and BML-190 from Tocris. HU-210 was a kind gift from Prof. R. Mechoulam, Hebrew University of Jerusalem, and SR14176A and SR144528 were donated by Sanofi Recherche. Indomethacin N-methyl-ester was obtained from Sigma. VDM-11, VDM-13, and arachidonoyl-serotonin were synthesized from the corresponding amines and arachidonoyl-chloride, as described previously.21
Biopsy
Biopsy specimens were obtained in agreement with
Endocannabinoid levels and CB1, CB2, and FAAH expression in human colorectal tissues
We found that human colon mucosa tissues contain both AEA and 2-AG (Figure 1A) , as determined by using an ultrasensitive LC-MS technique, and express mRNA transcripts of the size expected for CB1 and CB2 receptors as well as FAAH (Figure 1B), as determined by RT-PCR. The finding of CB1 receptors was also confirmed by Western immunoblot of proteins from biopsy specimens of normal colon mucosa (not shown). The levels of both AEA and 2-AG increased when passing from normal mucosa to transformed
Discussion
We found that human colon mucosa tissues contain both AEA and 2-AG and express CB1 and CB2 receptors as well as FAAH. The endocannabinoids and FAAH previously have been described to occur in mouse and rat whole colon,24, 25 but we found here that the levels of both AEA and 2-AG increase dramatically when passing from normal mucosa to adenomatous polyps and then slightly decrease in CRC tissue. These changes are likely to result in corresponding changes in endocannabinoid tissue concentrations.
Acknowledgements
The authors thank Drs. Filomena Fezza and Pierangelo Orlando for valuable assistance and Dr. Gabriella Caruso (I.R.C.C.S. “S. de Bellis,” Bari, Italy) for the kind gift of DLD-1 cells.
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Cited by (0)
- ☆
Supported by funds from the Italian National Research Council, MURST (3933 to V.D.M.) and the Associazione Italiana per la Ricerca sul Cancro (to M.B.).
- 1
A.L. and T.B. contributed equally to this work.