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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on November 14, 2003; DOI: 10.1124/jpet.103.061002

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Received for publication October 6, 2003.
Revised November 7, 2003.
Accepted for publication November 7, 2003.

Antitumor 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

* Address correspondence to: E-mail: daniela.parolaro{at}uninsubria.it

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 {alpha}-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


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