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Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines.
J Pharmacol Exp Ther. 2004 Mar; 308(3):838-45.JP

Abstract

Recently, cannabinoids (CBs) have been shown to possess antitumor properties. Because the psychoactivity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines. The addition of CBD to the culture medium led to a dramatic drop of mitochondrial oxidative metabolism [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide test] and viability in glioma cells, in a concentration-dependent manner that was already evident 24 h after CBD exposure, with an apparent IC(50) of 25 microM. The antiproliferative effect of CBD was partially prevented by the CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethylbicyclo[2,2,1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; SR2) and alpha-tocopherol. By contrast, the CB1 cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716; SR1), capsazepine (vanilloid receptor antagonist), the inhibitors of ceramide generation, or pertussis toxin did not counteract CBD effects. We also show, for the first time, that the antiproliferative effect of CBD was correlated to induction of apoptosis, as determined by cytofluorimetric analysis and single-strand DNA staining, which was not reverted by cannabinoid antagonists. Finally, CBD, administered s.c. to nude mice at the dose of 0.5 mg/mouse, significantly inhibited the growth of subcutaneously implanted U87 human glioma cells. In conclusion, the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent.

Authors+Show Affiliations

Department of Pharmacology, University of Milan, Milan, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

14617682

Citation

Massi, Paola, et al. "Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, On Human Glioma Cell Lines." The Journal of Pharmacology and Experimental Therapeutics, vol. 308, no. 3, 2004, pp. 838-45.
Massi P, Vaccani A, Ceruti S, et al. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. J Pharmacol Exp Ther. 2004;308(3):838-45.
Massi, P., Vaccani, A., Ceruti, S., Colombo, A., Abbracchio, M. P., & Parolaro, D. (2004). Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. The Journal of Pharmacology and Experimental Therapeutics, 308(3), 838-45.
Massi P, et al. Antitumor Effects of Cannabidiol, a Nonpsychoactive Cannabinoid, On Human Glioma Cell Lines. J Pharmacol Exp Ther. 2004;308(3):838-45. PubMed PMID: 14617682.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. AU - Massi,Paola, AU - Vaccani,Angelo, AU - Ceruti,Stefania, AU - Colombo,Arianna, AU - Abbracchio,Maria P, AU - Parolaro,Daniela, Y1 - 2003/11/14/ PY - 2003/11/18/pubmed PY - 2004/4/7/medline PY - 2003/11/18/entrez SP - 838 EP - 45 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 308 IS - 3 N2 - Recently, cannabinoids (CBs) have been shown to possess antitumor properties. Because the psychoactivity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines. The addition of CBD to the culture medium led to a dramatic drop of mitochondrial oxidative metabolism [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide test] and viability in glioma cells, in a concentration-dependent manner that was already evident 24 h after CBD exposure, with an apparent IC(50) of 25 microM. The antiproliferative effect of CBD was partially prevented by the CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethylbicyclo[2,2,1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; SR2) and alpha-tocopherol. By contrast, the CB1 cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716; SR1), capsazepine (vanilloid receptor antagonist), the inhibitors of ceramide generation, or pertussis toxin did not counteract CBD effects. We also show, for the first time, that the antiproliferative effect of CBD was correlated to induction of apoptosis, as determined by cytofluorimetric analysis and single-strand DNA staining, which was not reverted by cannabinoid antagonists. Finally, CBD, administered s.c. to nude mice at the dose of 0.5 mg/mouse, significantly inhibited the growth of subcutaneously implanted U87 human glioma cells. In conclusion, the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/14617682/Antitumor_effects_of_cannabidiol_a_nonpsychoactive_cannabinoid_on_human_glioma_cell_lines_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=14617682 DB - PRIME DP - Unbound Medicine ER -