Document Detail

Anti-proliferative effect of a putative endocannabinoid, 2-arachidonylglyceryl ether in prostate carcinoma cells.
MedLine Citation:
PMID:  21167293     Owner:  NLM     Status:  MEDLINE    
Endocannabinoids (ECs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), inhibit proliferation of carcinoma cells. Several enzymes hydrolyze ECs to reduce endogenous EC concentrations and produce eicosanoids that promote cell growth. In this study, we determined the effects of EC hydrolysis inhibitors and a putative EC, 2-arachidonylglyceryl ether (noladin ether, NE) on proliferation of prostate carcinoma (PC-3, DU-145, and LNCaP) cells. PC-3 cells had the least specific hydrolysis activity for AEA and administration of AEA effectively inhibited cell proliferation. The proliferation inhibition was blocked by SR141716A (a selective CB1R antagonist) but not SR144528 (a selective CB2R antagonist), suggesting a CB1R-mediated inhibition mechanism. On the other hand, specific hydrolysis activity for 2-AG was high and 2-AG inhibited proliferation only in the presence of EC hydrolysis inhibitors. NE inhibited proliferation in a concentration-dependent manner; however, SR141716A, SR144528 and pertussis toxin did not block the NE-inhibited proliferation, suggesting a CBR-independent mechanism of NE. A peroxisome proliferator-activated receptor gamma (PPARγ) antagonist GW9662 did not block the NE-inhibited proliferation, suggesting that PPARγ was not involved. NE also induced cell cycle arrest in G(0)/G(1) phase in PC-3 cells. NE inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB p65) and down-regulated the expression of cyclin D1 and cyclin E in PC-3 cells, suggesting the NF-κB/cyclin D and cyclin E pathways are involved in the arrest of G1 cell cycle and inhibition of cell growth. These results indicate therapeutic potentials of EC hydrolysis inhibitors and the enzymatically stable NE in prostate cancer.
Kasem Nithipatikom; Marilyn A Isbell; Michael P Endsley; Jeffrey E Woodliff; William B Campbell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-12-15
Journal Detail:
Title:  Prostaglandins & other lipid mediators     Volume:  94     ISSN:  1098-8823     ISO Abbreviation:  Prostaglandins Other Lipid Mediat.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-02     Completed Date:  2011-06-28     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  9808648     Medline TA:  Prostaglandins Other Lipid Mediat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34-43     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Anilides / pharmacology
Antineoplastic Agents / pharmacology*
Cannabinoid Receptor Modulators / pharmacology*
Cell Line, Tumor
Cell Proliferation
Cyclin D1 / metabolism
Cyclin E / metabolism
Glycerides / pharmacology*
NF-kappa B / metabolism
PPAR gamma / antagonists & inhibitors,  metabolism
Prostate / pathology
Prostatic Neoplasms / metabolism*,  pathology
Grant Support
Reg. No./Substance:
0/2-chloro-5-nitrobenzanilide; 0/Anilides; 0/Antineoplastic Agents; 0/Cannabinoid Receptor Modulators; 0/Cyclin E; 0/Endocannabinoids; 0/Glycerides; 0/NF-kappa B; 0/PPAR gamma; 0/noladin ether; 136601-57-5/Cyclin D1

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