title: The CB1 receptor antagonist rimonabant controls cell viability and ascitic tumour growth in mice.
abstract: Emerging findings suggested the efficacy of the cannabinoid CB1 receptor antagonist rimonabant (SR141716) in several pathological conditions included tumours. In this study we investigated in vitro the effects of SR141716 on viability and the molecular pathways of methylcholanthrene-induced fibrosarcoma (Meth-A) cells and in vivo its anti-tumour properties in Meth-A-bearing mice. We evaluated in vitro the effect of SR141716 on Meth-A cell viability by trypan blue staining assay. Cell cycle progression and apoptosis were assessed by flow cytometry. Protein expression was investigated by Western blot. The anti-tumour efficacy of SR141716 was evaluated in vivo monitoring weight increase and survival of Meth-A injected mice. SR141716 affects Meth-A cell viability inducing apoptosis and controls cell cycle progression by modulation of the levels of the cell cycle inhibitor p21waf, cyclins E, D1 and NF-kB molecules. Importantly, SR141716 affects AKT/pFoxO1 pathway which promotes cell survival and regulates the cell cycle. The molecular effects observed are accompanied by reduced COX2 expression and induction of the CB1 receptor expression. Finally, SR141716 was able to reduce the tumour size and prolong animal survival, when administered in vivo during tumour growth. Our findings shed light on a novel molecular pathway associated with control of tumour growth by SR141716 and confirm the anti-cancer and anti-inflammatory properties of this drug suggesting its potential applications in the treatment of cancer.
authors: Department of Pharmaceutical and Biomedical Sciences, University of Salerno, Via Ponte don Melillo, 84084 Fisciano, Salerno, Italy.
authors: Anna Maria
authors: AM
authors: Malfitano
authors: Chiara
authors: C
authors: Laezza
authors: Mario
authors: M
authors: Galgani
authors: Giuseppe
authors: G
authors: Matarese
authors: Alba
authors: A
authors: D'Alessandro
authors: Patrizia
authors: P
authors: Gazzerro
authors: Maurizio
authors: M
authors: Bifulco
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001201:Ascites / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D012509:Sarcoma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant