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Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol.

Abstract

PURPOSE

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.

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  • Authors+Show Affiliations

    ,

    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.

    ,

    Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy.

    ,

    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.

    ,

    School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom.

    Department of Pharmacy, University of Naples Federico II, Naples, Italy; Endocannabinoid Research Group, Italy. Electronic address: aaizzo@unina.it.

    Source

    MeSH

    Animals
    Azoxymethane
    CHO Cells
    Cannabidiol
    Cannabinoid Receptor Antagonists
    Cannabis
    Carcinogenesis
    Carcinoma
    Cell Proliferation
    Cell Survival
    Colonic Neoplasms
    Cricetinae
    Cricetulus
    Epithelial Cells
    HCT116 Cells
    Humans
    Male
    Mice, Inbred ICR
    Phytotherapy
    Plant Extracts
    Random Allocation
    Receptors, Cannabinoid
    Xenograft Model Antitumor Assays

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24373545

    Citation

    Romano, Barbara, et al. "Inhibition of Colon Carcinogenesis By a Standardized Cannabis Sativa Extract With High Content of Cannabidiol." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 21, no. 5, 2014, pp. 631-9.
    Romano B, Borrelli F, Pagano E, et al. Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. Phytomedicine. 2014;21(5):631-9.
    Romano, B., Borrelli, F., Pagano, E., Cascio, M. G., Pertwee, R. G., & Izzo, A. A. (2014). Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 21(5), pp. 631-9. doi:10.1016/j.phymed.2013.11.006.
    Romano B, et al. Inhibition of Colon Carcinogenesis By a Standardized Cannabis Sativa Extract With High Content of Cannabidiol. Phytomedicine. 2014 Apr 15;21(5):631-9. PubMed PMID: 24373545.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol. AU - Romano,Barbara, AU - Borrelli,Francesca, AU - Pagano,Ester, AU - Cascio,Maria Grazia, AU - Pertwee,Roger G, AU - Izzo,Angelo A, Y1 - 2013/12/25/ PY - 2013/10/11/received PY - 2013/11/29/accepted PY - 2013/12/31/entrez PY - 2014/1/1/pubmed PY - 2014/12/17/medline KW - ?(9)-Tetrahydrocannabinol KW - Cancer cell growth KW - Cannabidiol KW - Cannabinoid receptors KW - Chemoprevention KW - Colorectal cancer SP - 631 EP - 9 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 21 IS - 5 N2 - PURPOSE: 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. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/24373545/Inhibition_of_colon_carcinogenesis_by_a_standardized_Cannabis_sativa_extract_with_high_content_of_cannabidiol_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(13)00472-8 DB - PRIME DP - Unbound Medicine ER -