Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer.
Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis. Thus, we investigated its possible chemopreventive effect in the model of colon cancer induced by azoxymethane (AOM) in mice. AOM treatment was associated with aberrant crypt foci (ACF, preneoplastic lesions), polyps, and tumour formation, up-regulation of phospho-Akt, iNOS and COX-2 and down-regulation of caspase-3. Cannabidiol-reduced ACF, polyps and tumours and counteracted AOM-induced phospho-Akt and caspase-3 changes. In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation in a CB(1)-, TRPV1- and PPARγ-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.
Department of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II, Naples, Italy.
Gabriella
G
Aviello
Barbara
B
Romano
Francesca
F
Borrelli
Raffaele
R
Capasso
Laura
L
Gallo
Fabiana
F
Piscitelli
Vincenzo
V
Di Marzo
Angelo A
AA
Izzo
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001397:Azoxymethane / Q000494:pharmacology; D018938:Caco-2 Cells; D002185:Cannabidiol / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D020552:Comet Assay; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D000970:Antineoplastic Agents; D002185:Cannabidiol; D001397:Azoxymethane