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The influence of monoacylglycerol lipase inhibition upon the expression of epidermal growth factor receptor in human PC-3 prostate cancer cells.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
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2014 (English)In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 7, 441-447 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
BioMed Central, 2014. Vol. 7, 441-447 p.
Keyword [en]
Prostate cancer; Epidermal growth factor; Cannabinoid receptor; Monoacylglycerol lipase
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-101346DOI: 10.1186/1756-0500-7-441OAI: oai:DiVA.org:umu-101346DiVA: diva2:798767
Available from: 2015-03-27 Created: 2015-03-27 Last updated: 2017-12-04Bibliographically approved

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Cipriano, MariateresaGouveia-Figueira, SandraPersson, EmmaNording, MalinFowler, Christopher
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PharmacologyDepartment of ChemistryDepartment of Radiation Sciences
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