title: 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.
authors: Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano (Salerno), Italy.
authors: Patrizia
authors: P
authors: Gazzerro
authors: Anna M
authors: AM
authors: Malfitano
authors: Maria Chiara
authors: MC
authors: Proto
authors: Antonietta
authors: A
authors: Santoro
authors: Simona
authors: S
authors: Pisanti
authors: Maria Gabriella
authors: MG
authors: Caruso
authors: Maria
authors: M
authors: Notarnicola
authors: Caterina
authors: C
authors: Messa
authors: Chiara
authors: C
authors: Laezza
authors: Gabriella
authors: G
authors: Misso
authors: Michele
authors: M
authors: Caraglia
authors: Maurizio
authors: M
authors: Bifulco
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D010880:Piperidines / Q000008:administration & dosage* / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage* / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D000077285:Rimonabant; D013997:Time Factors
chemical_list: D009944:Organoplatinum Compounds; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077150:Oxaliplatin; D000077285:Rimonabant