Corticosterone inhibits the expression of cannabinoid receptor‑1 and cannabinoid receptor agonist‑induced decrease in cell viability in glioblastoma cells

Abstract

The endocannabinoid system regulates physiological and pathological conditions, including inflammation and cancer. Recently, emotional and physical stressors were observed to be involved in impairing the endocannabinoid system, which was concomitant with an increase in serum corticosteroids. However, the influence of corticosteroids on the endocannabinoid system has yet to be completely elucidated. The present study investigated the effects of corticosterone, one of the corticosteroids, on the endocannabinoid system in malignant glioblastoma cells in vitro. U-87 MG cells derived from malignant glioblastoma were subjected to corticosterone stimulation and their viability, signal transduction, and endocannabinoid-related gene expression were examined. Corticosterone decreased the mRNA and protein expressions of cyclooxygenase-2. Of note, although endocannabinoids decreased cell viability, corticosterone inhibited the cannabinoid receptor agonist-induced decrease in cell viability by downregulating the mRNA and protein expressions of cannabinoid receptor 1 (CB1) in glioblastoma cells. These results suggest that corticosteroids modify the endocannabinoid system in glioblastoma cells, and a reduction in the beneficial anti-tumor effects of endocannabinoids through downregulation of the CB1 receptor by corticosterone may promote the malignant phenotype of glioblastoma. Ishikawa 920-8640;

Inflammation and cancer: friend or foe?

“…Elevated corticosteroids levels in serum have been linked to changes in the endocannabinoid system (Wamsteeker et al, 2010). Studies such as those conducted by Sugimoto et al (2019), suggest that corticosterone may counteract the beneficial antitumor effects of ECs by reducing CB1R activity in glioblastoma models, thus promoting cancer growth. Given that stress is common in many diseases and corticosteroids are commonly used in treating The interplay between arachidonic acid, endocannabinoids, and prostamides, along with drugs that modulate their expression, influences inflammatory-related diseases.…”

Endocannabinoidome and its role in neurological disorders-A comprehensive update of existing literature

“…Sugimoto, et al investigated the effects of corticosterone on the endocannabinoid system in malignant glioblastoma cells in vitro. They found corticosterone inhibited the CBR agonist-induced decrease in cell viability by downregulating the mRNA and protein expressions of CB1 in glioblastoma cells and thereby exhibit anti-tumor properties [176] Phytanoyl-CoA 2-hydroxylase-interacting protein-like gene PHYHIPL may be a target gene for the treatment and prognosis of GBM, good prognosis accompanied by upregulated PHYHIPL may be the result of retrograde endocannabinoid signaling and the cAMP signaling pathway [177].…”