| Anti-proliferative effect of a putative endocannabinoid, 2-arachidonylglyceryl ether in prostate carcinoma cells. | |
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MedLine Citation:
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PMID: 21167293 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Kasem Nithipatikom; Marilyn A Isbell; Michael P Endsley; Jeffrey E Woodliff; William B Campbell |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-12-15 |
Journal Detail:
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Title: Prostaglandins & other lipid mediators Volume: 94 ISSN: 1098-8823 ISO Abbreviation: Prostaglandins Other Lipid Mediat. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-02 Completed Date: 2011-06-28 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 9808648 Medline TA: Prostaglandins Other Lipid Mediat Country: United States |
Other Details:
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Languages: eng Pagination: 34-43 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. kasemn@mcw.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anilides
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pharmacology Antineoplastic Agents / pharmacology* Cell Line, Tumor Cell Proliferation Cyclin D1 / metabolism Cyclin E / metabolism Endocannabinoids / pharmacology* Glycerides / pharmacology* Humans Male NF-kappa B / metabolism PPAR gamma / antagonists & inhibitors, metabolism Prostate / pathology Prostatic Neoplasms / metabolism*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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DA 09155/DA/NIDA NIH HHS; R01 DA009155-13/DA/NIDA NIH HHS; R01 DA009155-14/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-chloro-5-nitrobenzanilide; 0/Anilides; 0/Antineoplastic Agents; 0/Cyclin E; 0/Endocannabinoids; 0/Glycerides; 0/NF-kappa B; 0/PPAR gamma; 0/noladin ether; 136601-57-5/Cyclin D1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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