The Journal of Pharmacology And Experimental Therapeutics, First published on November 14, 2003
Anti-tumor effects of cannabidiol, a non-psychotropic
cannabinoid, on human glioma cell lines
Paola Massi 1, Angelo Vaccani 2, Stefania Ceruti 3, Arianna Colombo 1, Maria Pia Abbracchio 3, Daniela Parolaro 4*
1 Dept. of Pharm. Chem. and Toxicol. University of Milan, Milan, Italy 2 Dept. of Sruct. & Funct. Biol. Center of Neuroscience, University of Insubria Busto Arsizio (VA) Ita 3 Dept. Pharmacol. Sci., Center of Excellence for neurodeg. diseases, Univ. of Milan, Milan Italy 4 University of Insubria
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Abstract: Recently, cannabinoids have been shown to possess antitumor properties. Because the psycho-activity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of CBD, a non- psychoactive 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 (MTT test) and viability in glioma cells, in a concentration-dependent manner, already evident 24 h after CBD exposure with an apparent IC50 of 25 µM. The antiproliferative effect of CBD was partially prevented by the CB2 receptor antagonist SR144528 and -tocopherol. By contrast, the CB1 cannabinoid receptor antagonist SR141716, capsazepine (vanilloid receptor antagonist), the inhibitors of ceramide generation or PTX 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 ssDNA 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. Concluding, the non-psychoactive 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.
Key words: antiproliferative effects, apoptosis, cannabidiol, chemotherapeutic agent, glioma cells, in vivo tumor regression.
Please also see here in from Spain The study's findings come just one month after a clinical review in the journal Nature Reviews Cancer suggested that cannabinoids' palliative effects in cancer patients and ability to inhibit the growth of certain types of malignant tumors make them a potentially desirable agents in the treatment of cancer.
*Industrial-Hemp has no psychoactive properties following definition of the European Economic Community (EEC); THC content is less than 0.3%. In general, low THC-seed varieties without psychoactive properties are those that have a THC content of less than 1%. (See also No-THC Hemp-seed.) THC= Delta-9 TetraHydroCannabinol.
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