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5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid.
J Neurochem. 2008 Feb; 104(4):1091-100.JN

Abstract

It has been recently reported that cannabidiol (CBD), a non-psychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation. However, the underlying biochemical mechanisms were not clarified. In the present study, we performed biochemical analysis of the effect of CBD both in vivo, by using glioma tumor tissues excised from nude mice, and in vitro, by using U87 glioma cells. In vivo exposure of tumor tissues to CBD significantly decreased the activity and content of 5-lipoxygenase (LOX, by approximately 40%), and of its end product leukotriene B4 (approximately 25%). In contrast cyclooxygenase (COX)-2 activity and content, and the amount of its end product prostaglandin E2, were not affected by CBD. In addition, in vivo treatment with CBD markedly stimulated (approximately 175%) the activity of fatty acid amide hydrolase (FAAH), the main anandamide-degrading enzyme, while decreasing anandamide content (approximately 30%) and binding to CB1 cannabinoid receptors (approximately 25%). In vitro pre-treatment of U87 glioma cells with MK-886, a specific 5-LOX inhibitor, significantly enhanced the antimitotic effect of CBD, whereas the pre-treatment with indomethacin (pan-COX inhibitor) or celecoxib (COX-2 inhibitor), did not alter CBD effect. The study of the endocannabinoid system revealed that CBD was able to induce a concentration-dependent increase of FAAH activity in U87 cells. Moreover, a significantly reduced growth rate was observed in FAAH-over-expressing U87 cells, compared to wild-type controls. In conclusion, the present investigation indicates that CBD exerts its antitumoral effects through modulation of the LOX pathway and of the endocannabinoid system, suggesting a possible interaction of these routes in the control of tumor growth.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

18028339

Citation

Massi, P, et al. "5-Lipoxygenase and Anandamide Hydrolase (FAAH) Mediate the Antitumor Activity of Cannabidiol, a Non-psychoactive Cannabinoid." Journal of Neurochemistry, vol. 104, no. 4, 2008, pp. 1091-100.
Massi P, Valenti M, Vaccani A, et al. 5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid. J Neurochem. 2008;104(4):1091-100.
Massi, P., Valenti, M., Vaccani, A., Gasperi, V., Perletti, G., Marras, E., Fezza, F., Maccarrone, M., & Parolaro, D. (2008). 5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid. Journal of Neurochemistry, 104(4), 1091-100.
Massi P, et al. 5-Lipoxygenase and Anandamide Hydrolase (FAAH) Mediate the Antitumor Activity of Cannabidiol, a Non-psychoactive Cannabinoid. J Neurochem. 2008;104(4):1091-100. PubMed PMID: 18028339.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid. AU - Massi,P, AU - Valenti,M, AU - Vaccani,A, AU - Gasperi,V, AU - Perletti,G, AU - Marras,E, AU - Fezza,F, AU - Maccarrone,M, AU - Parolaro,D, Y1 - 2007/11/17/ PY - 2007/11/22/pubmed PY - 2008/2/15/medline PY - 2007/11/22/entrez SP - 1091 EP - 100 JF - Journal of neurochemistry JO - J Neurochem VL - 104 IS - 4 N2 - It has been recently reported that cannabidiol (CBD), a non-psychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation. However, the underlying biochemical mechanisms were not clarified. In the present study, we performed biochemical analysis of the effect of CBD both in vivo, by using glioma tumor tissues excised from nude mice, and in vitro, by using U87 glioma cells. In vivo exposure of tumor tissues to CBD significantly decreased the activity and content of 5-lipoxygenase (LOX, by approximately 40%), and of its end product leukotriene B4 (approximately 25%). In contrast cyclooxygenase (COX)-2 activity and content, and the amount of its end product prostaglandin E2, were not affected by CBD. In addition, in vivo treatment with CBD markedly stimulated (approximately 175%) the activity of fatty acid amide hydrolase (FAAH), the main anandamide-degrading enzyme, while decreasing anandamide content (approximately 30%) and binding to CB1 cannabinoid receptors (approximately 25%). In vitro pre-treatment of U87 glioma cells with MK-886, a specific 5-LOX inhibitor, significantly enhanced the antimitotic effect of CBD, whereas the pre-treatment with indomethacin (pan-COX inhibitor) or celecoxib (COX-2 inhibitor), did not alter CBD effect. The study of the endocannabinoid system revealed that CBD was able to induce a concentration-dependent increase of FAAH activity in U87 cells. Moreover, a significantly reduced growth rate was observed in FAAH-over-expressing U87 cells, compared to wild-type controls. In conclusion, the present investigation indicates that CBD exerts its antitumoral effects through modulation of the LOX pathway and of the endocannabinoid system, suggesting a possible interaction of these routes in the control of tumor growth. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/18028339/5_Lipoxygenase_and_anandamide_hydrolase__FAAH__mediate_the_antitumor_activity_of_cannabidiol_a_non_psychoactive_cannabinoid_ L2 - https://doi.org/10.1111/j.1471-4159.2007.05073.x DB - PRIME DP - Unbound Medicine ER -