title: Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.
abstract: OBJECTIVE
  Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo.
  
  
  METHODS
  Proliferation was evaluated in colorectal carcinoma (DLD-1 and HCT116) as well as in healthy colonic cells using the MTT assay. CBD BDS binding was evaluated by its ability to displace [(3)H]CP55940 from human cannabinoid CB1 and CB2 receptors. In vivo, the effect of CBD BDS was examined on the preneoplastic lesions (aberrant crypt foci), polyps and tumours induced by the carcinogenic agent azoxymethane (AOM) as well as in a xenograft model of colon cancer in mice.
  
  
  RESULTS
  CBD BDS and CBD reduced cell proliferation in tumoral, but not in healthy, cells. The effect of CBD BDS was counteracted by selective CB1 and CB2 receptor antagonists. Pure CBD reduced cell proliferation in a CB1-sensitive antagonist manner only. In binding assays, CBD BDS showed greater affinity than pure CBD for both CB1 and CB2 receptors, with pure CBD having very little affinity. In vivo, CBD BDS reduced AOM-induced preneoplastic lesions and polyps as well as tumour growth in the xenograft model of colon cancer.
  
  
  CONCLUSIONS
  CBD BDS attenuates colon carcinogenesis and inhibits colorectal cancer cell proliferation via CB1 and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabis-based medicines in cancer patients.
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy; School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Barbara
authors.initials: B
authors.lastname: Romano
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Borrelli
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy.
authors.forename: Ester
authors.initials: E
authors.lastname: Pagano
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Cascio
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Pertwee
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy. Electronic address: aaizzo@unina.it.
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Izzo
mesh_terms: D000818:Animals; D001397:Azoxymethane; D016466:CHO Cells; D002185:Cannabidiol / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D063387:Cannabinoid Receptor Antagonists; D002188:Cannabis; D063646:Carcinogenesis / Q000187:drug effects; D002277:Carcinoma / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000517:prevention & control*; D006224:Cricetinae; D003412:Cricetulus; D004847:Epithelial Cells / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D043882:Receptors, Cannabinoid / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D063387:Cannabinoid Receptor Antagonists; D010936:Plant Extracts; D043882:Receptors, Cannabinoid; D002185:Cannabidiol; D001397:Azoxymethane
keywords: ?(9)-Tetrahydrocannabinol; Cancer cell growth; Cannabidiol; Cannabinoid receptors; Chemoprevention; Colorectal cancer