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Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines.

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.
AuthorsPaola Massi, Angelo Vaccani, Stefania Ceruti, Arianna Colombo, Maria P Abbracchio, Daniela Parolaro
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 308 Issue 3 Pg. 838-45 (Mar 2004) ISSN: 0022-3565 [Print] United States
PMID14617682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Cannabinoids
  • Receptors, Drug
  • Cannabidiol
  • Pertussis Toxin
Topics
  • Animals
  • Antineoplastic Agents (pharmacology, therapeutic use)
  • Apoptosis
  • Cannabidiol (pharmacology, therapeutic use)
  • Cannabinoids (pharmacology)
  • Cell Division (drug effects)
  • Cell Survival (drug effects)
  • Disease Models, Animal
  • Drug Interactions
  • Glioma (drug therapy, pathology)
  • Humans
  • Mice
  • Neoplasm Transplantation
  • Neoplasms, Experimental (drug therapy)
  • Pertussis Toxin (pharmacology)
  • Receptors, Drug (antagonists & inhibitors)
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

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