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Rimonabant (SR141716) exerts anti‐proliferative and immunomodulatory effects in human peripheral blood mononuclear cells
Author(s) -
Malfitano A M,
Laezza C,
Pisanti S,
Gazzerro P,
Bifulco M
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707651
Subject(s) - rimonabant , cannabinoid receptor , peripheral blood mononuclear cell , cell cycle , apoptosis , biology , cell growth , endocannabinoid system , protein kinase b , pharmacology , cancer research , endocrinology , medicine , receptor , antagonist , in vitro , biochemistry
Background and purpose: Rimonabant (SR141716) is the first selective cannabinoid receptor CB 1 antagonist described. Along with its anti‐obesity action, emerging findings show potential anti‐proliferative and anti‐inflammatory action of SR141716 in several in vitro and in vivo models. In this study we have investigated the anti‐proliferative and immunomodulatory effects of SR141716 in human peripheral blood mononuclear cells (PBMCs). Experimental approach: We have evaluated in vitro the effect of SR141716 in human PBMCs stimulated with different mitogens. Cell proliferation was assessed by 3 H‐thymidine incorporation. Cell cycle, cell death and apoptosis were analysed by flow cytometry. Protein expression was investigated by Western blot. Key results: SR141716 significantly inhibited the proliferative response of PBMCs and this effect was accompanied by block of G 1 /S phase of the cell cycle without induction of apoptosis and cell death. SR141716 used in combination with 2‐methyl‐arachidonyl‐2′‐fluoro‐ethylamide (Met‐F‐AEA), a stable analogue of the endogenous cannabinoid anandamide, showed synergism rather than antagonism of the inhibition of cell proliferation. The immunomodulatory effects of SR141716 were associated with increased expression of IκB, phosphorylated AKT (p‐AKT) and decreased expression of NF‐κB, p‐IκB, p‐ERK, COX‐2 and iNOS. Conclusions and implications: Our findings suggest SR141716 is a novel immunomodulatory drug with anti‐inflammatory properties. British Journal of Pharmacology (2008) 153 , 1003–1010; doi: 10.1038/sj.bjp.0707651 ; published online 24 December 2007