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Synergistic inhibition of human colon cancer cell growth by the cannabinoid CB1 receptor antagonist rimonabant and oxaliplatin.

Abstract
Rimonabant (SR141716), a highly selective cannabinoid receptor antagonist, exerts along with its anti-obesity action, pleiotropic functions affecting a broad range of diseases, from obesity-related co-morbidities to drug dependence and cancer. Several studies suggested an anti-tumour activity of rimonabant in several in vitro and in vivo models. In this study, we compared the anti-proliferative effect of SR141716 in the human colon cancer cell line DLD-1 with oxaliplatin, one of the cytotoxic drugs currently used in the treatment of colorectal cancer. We show that SR141716 inhibits DLD-1 cell proliferation similarly to oxaliplatin and if administered in combination SR141716 potentiated the inhibitory effect caused by oxaliplatin. Assessment of drug interaction was performed calculating combination index that showed a strong synergistic effect between the two drugs added to cells in combination. Our findings suggest that the combined synergic effect of SR141716 and oxaliplatin improves the blocking of colon cancer cell proliferation. Therefore, this combination merits further explorations in preclinical and clinical settings.
AuthorsPatrizia Gazzerro, Anna M Malfitano, Maria Chiara Proto, Antonietta Santoro, Simona Pisanti, Maria Gabriella Caruso, Maria Notarnicola, Caterina Messa, Chiara Laezza, Gabriella Misso, Michele Caraglia, Maurizio Bifulco
JournalOncology reports (Oncol Rep) Vol. 23 Issue 1 Pg. 171-5 (Jan 2010) ISSN: 1791-2431 [Electronic] Greece
PMID19956878 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Organoplatinum Compounds
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Oxaliplatin
  • Rimonabant
Topics
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms (drug therapy, pathology)
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Humans
  • Organoplatinum Compounds (administration & dosage)
  • Oxaliplatin
  • Piperidines (administration & dosage, pharmacology)
  • Pyrazoles (administration & dosage, pharmacology)
  • Receptor, Cannabinoid, CB1 (antagonists & inhibitors, physiology)
  • Rimonabant
  • Time Factors

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