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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.

Cipriano M, Gouveia-Figueira S, Persson E, Nording M, Fowler CJ - BMC Res Notes (2014)

Bottom Line: CB1 receptor expression levels were found to differ greatly between two experimental series conducted using PC-3 cells.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden. cf@pharm.umu.se.

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.

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Effects of EGF and JZL184 upon CB1 receptor and EGFR expression in PC3 cells. Cells from the second experimental series were incubated with EGF and JZL184 as described in the legend to Figure 2. The EGFR mRNA is shown as a function of the CB1 receptor mRNA, both normalised to β-actin, for the second series cells, each data point being for a given well. Shown in each Panel are the Spearman rho values.
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Figure 5: Effects of EGF and JZL184 upon CB1 receptor and EGFR expression in PC3 cells. Cells from the second experimental series were incubated with EGF and JZL184 as described in the legend to Figure 2. The EGFR mRNA is shown as a function of the CB1 receptor mRNA, both normalised to β-actin, for the second series cells, each data point being for a given well. Shown in each Panel are the Spearman rho values.

Mentions: For the low CB1 receptor-expressing PC-3 cells (i.e. the second experimental series), the effects of EGF and JZL184 upon EGFR expression were investigated (Figure 5) and linear regression analyses were performed. For these analyses, the data for CB1 receptor and EGFR expression were logged since residual plots of the regressions using untransformed data were not considered acceptable for parametric analysis (not shown). Using the logged data and with EGFR/β-actin as the dependent variable, the unstandardized coefficients obtained were: EGF, 0.019 ± 0.057, P > 0.7; JZL184, -0.12 ± 0.056, P < 0.05; CB1R, 0.31 ± 0.24, P > 0.2; interaction term EGF × CB1R, 0.078 ± 0.26, P > 0.7; interaction term JZL184 × CB1R, -0.72 ± 0.31, P < 0.05; interaction term EGF × JZL184 × CB1R, 0.46 ± 0.36, P > 0.2. The value of the constant was 0.31 ± 0.05 and the ANOVA for the regression was F6,35 = 2.89, P < 0.05. Inclusion of the interaction terms in the model increased the adjusted r2 value from 0.092 to 0.244.


The influence of monoacylglycerol lipase inhibition upon the expression of epidermal growth factor receptor in human PC-3 prostate cancer cells.

Cipriano M, Gouveia-Figueira S, Persson E, Nording M, Fowler CJ - BMC Res Notes (2014)

Effects of EGF and JZL184 upon CB1 receptor and EGFR expression in PC3 cells. Cells from the second experimental series were incubated with EGF and JZL184 as described in the legend to Figure 2. The EGFR mRNA is shown as a function of the CB1 receptor mRNA, both normalised to β-actin, for the second series cells, each data point being for a given well. Shown in each Panel are the Spearman rho values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4109781&req=5

Figure 5: Effects of EGF and JZL184 upon CB1 receptor and EGFR expression in PC3 cells. Cells from the second experimental series were incubated with EGF and JZL184 as described in the legend to Figure 2. The EGFR mRNA is shown as a function of the CB1 receptor mRNA, both normalised to β-actin, for the second series cells, each data point being for a given well. Shown in each Panel are the Spearman rho values.
Mentions: For the low CB1 receptor-expressing PC-3 cells (i.e. the second experimental series), the effects of EGF and JZL184 upon EGFR expression were investigated (Figure 5) and linear regression analyses were performed. For these analyses, the data for CB1 receptor and EGFR expression were logged since residual plots of the regressions using untransformed data were not considered acceptable for parametric analysis (not shown). Using the logged data and with EGFR/β-actin as the dependent variable, the unstandardized coefficients obtained were: EGF, 0.019 ± 0.057, P > 0.7; JZL184, -0.12 ± 0.056, P < 0.05; CB1R, 0.31 ± 0.24, P > 0.2; interaction term EGF × CB1R, 0.078 ± 0.26, P > 0.7; interaction term JZL184 × CB1R, -0.72 ± 0.31, P < 0.05; interaction term EGF × JZL184 × CB1R, 0.46 ± 0.36, P > 0.2. The value of the constant was 0.31 ± 0.05 and the ANOVA for the regression was F6,35 = 2.89, P < 0.05. Inclusion of the interaction terms in the model increased the adjusted r2 value from 0.092 to 0.244.

Bottom Line: CB1 receptor expression levels were found to differ greatly between two experimental series conducted using PC-3 cells.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden. cf@pharm.umu.se.

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.

Show MeSH
Related in: MedlinePlus