Original Article

Journal of Molecular Medicine

, Volume 90, Issue 8, pp 925-934

First online:

Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer

  • Gabriella AvielloAffiliated withDepartment of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II
  • , Barbara RomanoAffiliated withDepartment of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II
  • , Francesca BorrelliAffiliated withDepartment of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II
  • , Raffaele CapassoAffiliated withDepartment of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico II
  • , Laura GalloAffiliated withInstitute of Biomolecular Chemistry, Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche (CNR)
  • , Fabiana PiscitelliAffiliated withInstitute of Biomolecular Chemistry, Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche (CNR)
  • , Vincenzo Di MarzoAffiliated withInstitute of Biomolecular Chemistry, Endocannabinoid Research Group, Consiglio Nazionale delle Ricerche (CNR)Institute of Biomolecular Chemistry, CNR Email author 
  • , Angelo A. IzzoAffiliated withDepartment of Experimental Pharmacology, Endocannabinoid Research Group, University of Naples Federico IIDepartment of Experimental Pharmacology, University of Naples Federico II Email author 

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Abstract

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 CB1-, TRPV1- and PPARγ-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.

Keywords

Non-psychotropic cannabinoid Colon cancer Adenocarcinoma cells DNA damage