title: The influence of monoacylglycerol lipase inhibition upon the expression of epidermal growth factor receptor in human PC-3 prostate cancer cells.
abstract: BACKGROUND
  It has been reported that direct activation of the cannabinoid CB1 receptor in epidermal growth factor (EGR)-stimulated PC-3 prostate cancer cells results in an anti-proliferative effect accompanied by a down-regulation of EGF receptors (EGFR). In the present study, we investigated whether similar effects are seen following inhibition of the endocannabinoid hydrolytic enzyme monoacylglycerol lipase (MGL).
  
  
  RESULTS
  CB1 receptor expression levels were found to differ greatly between two experimental series conducted using PC-3 cells. The monoacylglycerol lipase inhibitor JZL184 increased levels of 2-arachidonoylglycerol in the PC-3 cells without producing changes in the levels of anandamide and related N-acylethanolamines. In the first series of experiments, JZL184 produced a small mitogenic effect for cells that had not been treated with EGF, whereas an anti-proliferative effect was seen for EGF-treated cells. An anti-proliferative effect for the EGF-treated cells was also seen with the CB receptor agonist CP55,940. In the second batch of cells, there was an interaction between JZL184 and CB1 receptor expression densities in linear regression analyses with EGFR expression as the dependent variable.
  
  
  CONCLUSIONS
  Inhibition of MGL by JZL184 can affect EGFR expression. However, the use in our hands of PC-3 cells as a model to investigate the therapeutic potential of MGL inhibitors and related compounds is compromised by their variability of CB1 receptor expression.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Cipriano
authors.forename: Sandra
authors.initials: S
authors.lastname: Gouveia-Figueira
authors.forename: Emma
authors.initials: E
authors.lastname: Persson
authors.forename: Malin
authors.initials: M
authors.lastname: Nording
authors.affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden. cf@pharm.umu.se.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Fowler
mesh_terms: D001095:Arachidonic Acids / Q000378:metabolism; D052117:Benzodioxoles / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003511:Cyclohexanols / Q000494:pharmacology; D063388:Endocannabinoids / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005989:Glycerides / Q000378:metabolism; D006801:Humans; D008297:Male; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001095:Arachidonic Acids; D052117:Benzodioxoles; D002186:Cannabinoids; D003511:Cyclohexanols; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D005989:Glycerides; C534333:JZL 184; C022203:N-acylethanolamines; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; C094503:glyceryl 2-arachidonate; D066246:ErbB Receptors; D008994:Monoacylglycerol Lipases; C078814:anandamide