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

Barbara Romano; Francesca Borrelli; Ester Pagano; Maria Grazia Cascio; Roger G. Pertwee; Angelo A. Izzo

doi:10.1016/j.phymed.2013.11.006

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

Barbara Romano, Francesca Borrelli, Ester Pagano, Maria Grazia Cascio, Roger G. Pertwee, Angelo A. Izzo^*

^*Corresponding author for this work

Medical Sciences

Research output: Contribution to journal › Article › peer-review

90 Citations (Scopus)

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 MU assay. CBD BDS binding was evaluated by its ability to displace [H-3]CP55940 from human cannabinoid CBI 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 CBI 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 CBI and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabisbased medicines in cancer patients. (c) 2013 Elsevier GmbH. All rights reserved.

Original language	English
Pages (from-to)	631-639
Number of pages	9
Journal	Phytomedicine
Volume	21
Issue number	5
Early online date	25 Dec 2013
DOIs	https://doi.org/10.1016/j.phymed.2013.11.006
Publication status	Published - 15 Apr 2014

Bibliographical note

Conflict of interest
This investigation was partly supported by grants from GW Pharmaceuticals (Porton Down, Wiltshire, UK).

Acknowledgement
BR is grateful to the “Fondazione Enrico & Enrica Sovena”

Keywords

Cannabinoid receptors
Cannabidiol
Delta(9)-Tetrahydrocannabinol
Cancer cell growth
Chemoprevention
Colorectal cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.phymed.2013.11.006Licence: Unspecified

Cite this

@article{3347359c61fd48bea3ab87740367e0db,

title = "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 MU assay. CBD BDS binding was evaluated by its ability to displace [H-3]CP55940 from human cannabinoid CBI 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 CBI 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 CBI and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabisbased medicines in cancer patients. (c) 2013 Elsevier GmbH. All rights reserved.",

keywords = "Cannabinoid receptors, Cannabidiol, Delta(9)-Tetrahydrocannabinol, Cancer cell growth, Chemoprevention, Colorectal cancer",

author = "Barbara Romano and Francesca Borrelli and Ester Pagano and Cascio, {Maria Grazia} and Pertwee, {Roger G.} and Izzo, {Angelo A.}",

note = "Conflict of interest This investigation was partly supported by grants from GW Pharmaceuticals (Porton Down, Wiltshire, UK). Acknowledgement BR is grateful to the “Fondazione Enrico & Enrica Sovena”",

year = "2014",

month = apr,

day = "15",

doi = "10.1016/j.phymed.2013.11.006",

language = "English",

volume = "21",

pages = "631--639",

journal = "Phytomedicine",

issn = "0944-7113",

publisher = "ELSEVIER GMBH, URBAN & FISCHER VERLAG",

number = "5",

}

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.

N1 - Conflict of interest This investigation was partly supported by grants from GW Pharmaceuticals (Porton Down, Wiltshire, UK). Acknowledgement BR is grateful to the “Fondazione Enrico & Enrica Sovena”

PY - 2014/4/15

Y1 - 2014/4/15

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 MU assay. CBD BDS binding was evaluated by its ability to displace [H-3]CP55940 from human cannabinoid CBI 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 CBI 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 CBI and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabisbased medicines in cancer patients. (c) 2013 Elsevier GmbH. All rights reserved.

AB - 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 MU assay. CBD BDS binding was evaluated by its ability to displace [H-3]CP55940 from human cannabinoid CBI 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 CBI 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 CBI and CB2 receptor activation. The results may have some clinical relevance for the use of Cannabisbased medicines in cancer patients. (c) 2013 Elsevier GmbH. All rights reserved.

KW - Cannabinoid receptors

KW - Cannabidiol

KW - Delta(9)-Tetrahydrocannabinol

KW - Cancer cell growth

KW - Chemoprevention

KW - Colorectal cancer

U2 - 10.1016/j.phymed.2013.11.006

DO - 10.1016/j.phymed.2013.11.006

M3 - Article

SN - 0944-7113

VL - 21

SP - 631

EP - 639

JO - Phytomedicine

JF - Phytomedicine

IS - 5

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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