Orexin A Suppresses the Growth of Rat C6 Glioma Cells via a Caspase-Dependent Mechanism

Abstract

Orexin A and orexin B (also known as hypocretins) are closely related peptides synthesized by hypothalamic neurons. They orchestrate diverse central and peripheral processes by stimulation of two G-protein coupled receptors, OX1R and OX2R. Recent studies have demonstrated the ability of orexins to promote a robust apoptosis in different cancer cells in culture and a potent growth reduction of human colon tumors in mice xenografts. Here we report effects of orexins on survival of rat C6 glioma cells, an experimental model for studies on glioblastoma multiforme (GBM). Quantitative real-time PCR demonstrated the expression of both types of orexin receptors in C6 cells. Orexin A and orexin B did not affect rat C6 glioma cell proliferation as assessed by [3H]thymidine incorporation assay. Incubation of the cells with orexin A (0.001–1 μM) resulted in a marked decrease of cell viability. The observed effect was caspase-dependent, as it was blocked by Z-VAD-fmk, a pan caspase inhibitor. In addition to that, a parallel increase in caspase-3 activity was observed. It is suggested that stimulation of orexin receptors induces death of rat C6 glioma cells through activation of caspase pathway.

Orexin-A stimulates 3β-hydroxysteroid dehydrogenase expression and cortisol production in H295R human adrenocortical cells through the AKT pathway

“…However, data on whether orexins regulate the growth of carcinoma cells are inconlcusive. Certain studies have found that orexins promote the growth of cancer cells (8,10), athough others have shown inhibitory effects (30,31). The different cell types used may be the reason for these conflicting results.…”

Orexin A upregulates the protein expression of OX1R and enhances the proliferation of SGC-7901 gastric cancer cells through the ERK signaling pathway

“…OX2R mRNA was expressed in rat pancreatic acinar tumor line AR42J (13). OX1R and OX2R were detected in rat C6 glioma cells (14). These cell lines exhibited decreased cell division and increased cell death upon orexin exposure.…”

“…Orexin A can induce apoptosis via OX2R in rat pancreatic tumor cells involving the caspase-3 and caspase-9 pathway (13). A study also found that orexin A induces p38/mitogen-activated protein kinase (MAPK)-and caspase-dependent cell death in rat C6 glioma cells (14).…”

“…Apart from its roles in regulating central and peripheral actions, orexins have been previously highlighted in cancer cells (11)(12)(13)(14). Orexins, acting at OX1R or OX2R, result in strong apoptosis and a decrease of cell growth in diverse cancer cell lines, including human colon cancer cells (11,12), human neuroblastoma cells (11), rat pancreatic tumor cells (13) and rat C6 glioma cells (14). Studies have shown that orexins promote strong apoptosis in human colon cancer cells through OX1R by inducing the release of cytochrome c from mitochondria and activation of caspase-3/7 (12).…”

Identification of valid endogenous control genes for determining gene expression in C6 glioma cell line treated with conditioned medium from adipose-derived stem cell

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