Corticosterone Inhibits the Proliferation of C6 Glioma Cells <i>via</i> the Translocation of Unphosphorylated Glucocorticoid Receptor

Abstract

Astroglial cells have been considered to have passive brain function by helping to maintain neurons.However, recent studies have revealed that the dysfunction of such passive functions may be associated with various neuropathological diseases, such as schizophrenia, Alzheimer's disease, amyotrophic lateral sclerosis and major depression. Corticosterone (CORT), which is often referred to as the stress hormone, is a well-known regulator of peripheral immune responses and also shows anti-inflammatory properties in the brain. However, it is still obscure how CORT affects astroglial cell function. In this study, we investigated the effects of CORT on the proliferation and survival of astroglial cells using C6 glioma cells. Under treatment with CORT for 24h, the proliferation of C6 glioma cells decreased in a dose-dependent manner. Moreover, this inhibition was diminised by treatment with mifepristone, a glucocorticoid receptor (GR) antagonist, but not by spironolactone, a mineralocorticoid receptor (MR) antagonist, and was independent of GR phosphorylation and other GR-related intracellular signaling cascades. Furthermore, it was observed that the translocation of GR from the cytosol to the nucleus was promoted by the treatment with CORT. These results indicate that CORT decreases the proliferation of C6 glioma cells by modifying the transcription of a particular gene related to cell proliferation independent of GR phosphorylation.

Astrocytoma: A Hormone-Sensitive Tumor?

“…A recent study indicated that treatment with cortisone for 24 h resulted in a decrease in the proliferation of C6 cells in a dose-dependent manner due to the translocation of GR in the nucleus. These effects were GR dependent since the addition of mifepristone, a GR antagonist blocked the effect of cortisone [95]. No clinical studies addressed the specific role of either GRα or GRβ isoforms or mineralocorticoid receptors that are both expressed in glioma cells, although this could help to understand the precise mechanism of action of dexamethasone or other corticoids.…”

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

“…Nakatani et al (24), showed that corticosterone inhibited the proliferation of C6 glioma cells. However, in our present study, corticosterone did not inhibit the cell viability in U-87 MG cells.…”

Fluoxetine triggers selective apoptosis in inflammation‐induced proliferating (Ki‐67high) thymocytes

“…However, the specific mechanism by which NFκB blocks p53 activity during low‐grade inflammation is not well documented. Several important molecules have been targeted in order to inhibit the proliferative transitions in cancer cells, one such molecule being corticosterone, a stress hormone that acts through the glucocorticoid receptor pathway and is a well‐known regulator of peripheral immune responses showing anti‐inflammatory/proliferative properties . Furthermore, it is known that overexpression of glucocorticoid‐induced tumor necrosis factor (TNF) receptor function retards proliferation in multiple myeloma cells through the modulation of NFκB and p53 proteins …”

“…Several important molecules have been targeted in order to inhibit the proliferative transitions in cancer cells, one such molecule being corticosterone, a stress hormone that acts through the glucocorticoid receptor pathway and is a well-known regulator of peripheral immune responses showing antiinflammatory/proliferative properties. 17 Furthermore, it is known that overexpression of glucocorticoid-induced tumor necrosis factor (TNF) receptor function retards proliferation in multiple myeloma cells through the modulation of NFjB and p53 proteins. 18 It has been reported previously that, fluoxetine, a selective serotonin reuptake inhibitor, is able to act as an anticancer agent by virtue of its ability to reduce acute murine colitis through inhibition of the NFjB pathway.…”