Title |
Increased endocannabinoid levels reduce the development of precancerous lesions in the mouse colon
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Published in |
Journal of Molecular Medicine, September 2007
|
DOI | 10.1007/s00109-007-0248-4 |
Pubmed ID | |
Authors |
Angelo A. Izzo, Gabriella Aviello, Stefania Petrosino, Pierangelo Orlando, Giovanni Marsicano, Beat Lutz, Francesca Borrelli, Raffaele Capasso, Santosh Nigam, Francesco Capasso, Vincenzo Di Marzo, Endocannabinoid Research Group |
Abstract |
Colorectal cancer is an increasingly important cause of death in Western countries. Endocannabinoids inhibit colorectal carcinoma cell proliferation in vitro. In this paper, we investigated the involvement of endocannabinoids on the formation of aberrant crypt foci (ACF, earliest preneoplastic lesions) in the colon mouse in vivo. ACF were induced by azoxymethane (AOM); fatty acid amide hydrolase (FAAH) and cannabinoid receptor messenger ribonucleic acid (mRNA) levels were analyzed by the quantitative reverse transcription polymerase chain reaction (RT-PCR); endocannabinoid levels were measured by liquid chromatography-mass spectrometry; caspase-3 and caspase-9 expressions were measured by Western blot analysis. Colonic ACF formation after AOM administration was associated with increased levels of 2-arachidonoylglycerol (with no changes in FAAH and cannabinoid receptor mRNA levels) and reduction in cleaved caspase-3 and caspase-9 expression. The FAAH inhibitor N-arachidonoylserotonin increased colon endocannabinoid levels, reduced ACF formation, and partially normalized cleaved caspase-3 (but not caspase-9) expression. Notably, N-arachidonoylserotonin completely prevented the formation of ACF with four or more crypts, which have been show to be best correlated with final tumor incidence. The effect of N-arachidonoylserotonin on ACF formation was mimicked by the cannabinoid receptor agonist HU-210. No differences in ACF formation were observed between CB(1) receptor-deficient and wild-type mice. It is concluded that pharmacological enhancement of endocannabinoid levels (through inhibition of endocannabinoid hydrolysis) reduces the development of precancerous lesions in the mouse colon. The protective effect appears to involve caspase-3 (but not caspase-9) activation. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 1% |
Czechia | 1 | 1% |
Unknown | 65 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 15 | 22% |
Student > Ph. D. Student | 10 | 15% |
Student > Master | 8 | 12% |
Student > Doctoral Student | 6 | 9% |
Student > Bachelor | 5 | 7% |
Other | 13 | 19% |
Unknown | 10 | 15% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 14 | 21% |
Pharmacology, Toxicology and Pharmaceutical Science | 10 | 15% |
Biochemistry, Genetics and Molecular Biology | 9 | 13% |
Agricultural and Biological Sciences | 9 | 13% |
Chemistry | 6 | 9% |
Other | 5 | 7% |
Unknown | 14 | 21% |