Synergistic inhibition of human colon cancer cell growth by the cannabinoid CB1 receptor antagonist rimonabant and oxaliplatin.
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.
Gazzerro
Patrizia
P
Dipartimento di Scienze Farmaceutiche, Università di Salerno, Fisciano (Salerno), Italy.
Malfitano
Anna M
AM
Proto
Maria Chiara
MC
Santoro
Antonietta
A
Pisanti
Simona
S
Caruso
Maria Gabriella
MG
Notarnicola
Maria
M
Messa
Caterina
C
Laezza
Chiara
C
Misso
Gabriella
G
Caraglia
Michele
M
Bifulco
Maurizio
M
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
D009944:Organoplatinum Compounds; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077150:Oxaliplatin; D000077285:Rimonabant