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Urbanhog moderator


Joined: 22 Apr 2003 Posts: 338 Location: Tropical Queensland, Australia
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Posted: Thu Oct 02, 2003 3:30 am Post subject: Cannabinoids seen as potential colorectal tumor inhibitors |
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Endogenous cannabinoids seen as potential colorectal tumor inhibitors
Reuters Health
Posting Date: September 29, 2003
Last Updated: 2003-09-29 10:09:29 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Endogenous cannabinoids inhibit colorectal carcinoma proliferation, new research suggests. Activating or curbing the inactivation of the endocannabinoid system might represent a potential new anticancer strategy, the authors say.
"Endocannabinoids, the endogenous ligands for the receptors of marijuana's psychoactive principle THC, seemingly play an important regulatory role under pathological conditions," Dr. Vincenzo Di Marzo from the Institute of Biomolecular Chemistry, C.N.R., in Pozzuoli, Italy, told Reuters Health.
The endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), and their receptors have previously been shown to inhibit the proliferation of breast and prostate cancer cells and rat thyroid cancer cells.
Dr. Di Marzo and colleagues determined levels of anandamide and 2-AG, the cannabinoid receptors CB1 and CB2, and fatty acid amide hydrolase (FAAH), which catalyzes endocannabinoid hydrolysis, in colorectal carcinoma, adenomatous polyps, and healthy surrounding mucosa obtained from 21 patients by biopsy during colonoscopy.
All samples contained anandamide, 2-AG, cannabinoid receptors, and FAAH, they report.
Of note, the levels of 2-AG and anandamide, but not CB1, CB2, or FAAH, were significantly elevated in cancerous and, particularly, precancerous colonic tissue relative to neighboring healthy mucosa.
"Endocannabinoids are enhanced in transformed colon mucosa cells possibly to counteract proliferation via cannabinoid receptors," the team suggests in the September issue of the journal Gastroenterology.
"Levels of both anandamide and 2-AG increase dramatically when passing from normal mucosa to adenomatous polyps and then slightly decrease in CRC tissue," they further explain.
To see whether the endocannabinoid system affects colorectal carcinoma growth, they tested the effects of cannabinoids on undifferentiated and differentiated cultured CaCo-2 cells, which are widely used in colorectal cancer research.
Anandamide and 2-AG as well as selective CB1 receptor agonists "potently" inhibited the growth of undifferentiated CaCo-2 cells in a dose-dependent fashion but had little antiproliferative effect in differentiated CaCo-2 cells.
Pharmacologic inhibition of endocannabinoid inactivation also reduced proliferation of undifferentiated CaCo-2 cells and raised endocannabinoid levels.
These findings, Dr. Di Marzo said, open up the possibility of using inhibitors of endocannabinoid degradation to block certain types of cancer. His team already has some "promising evidence" for this strategy in an animal model of thyroid carcinoma.
"However, still a lot is to be done at the pre-clinical level before it is possible to suggest the use of agents that activate cannabinoid receptors directly (such as THC), or indirectly (such as these inhibitors of endocannabinoid degradation), in the clinic," he emphasized.
Dr. Steven R. Vigna of the VA Medical Center in Durham, North Carolina, writes in an editorial that as "putative inhibitors" of colorectal carcinoma, the potential therapeutic value of the gut endocannabinoid system "appears to be substantial."
Gastroenterology 2003;125:677-687,973-975. |
http://oncolink.upenn.edu/resources/article.cfm?c=3&s=8&ss=23&Year=2003&Month=09&id=10138
cheers, Urbie  _________________ "Travel is fatal to prejudice, bigotry, and narrow-mindedness, and many of our people need it sorely on these accounts. Broad, wholesome, charitable views of men and things cannot be acquired by vegetating in one little corner of the earth all one's lifetime."
--Mark Twain, The Innocents Abroad (1869) |
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