Orexin A suppresses the growth of rat C6 glioma cells via a caspase-dependent mechanism

J Mol Neurosci. 2012 Nov;48(3):706-12. doi: 10.1007/s12031-012-9799-0. Epub 2012 May 17.


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, OX(1)R and OX(2)R. 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 [(3)H]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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Caspase Inhibitors / pharmacology
  • Caspases / physiology*
  • Cell Division / drug effects
  • Cell Line, Tumor / chemistry
  • Cell Line, Tumor / drug effects
  • Glioma / pathology*
  • Intracellular Signaling Peptides and Proteins / pharmacology*
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / drug effects*
  • Neoplasm Proteins / genetics
  • Neuropeptides / pharmacology*
  • Orexin Receptors
  • Orexins
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Rats
  • Receptors, G-Protein-Coupled / analysis*
  • Receptors, G-Protein-Coupled / biosynthesis
  • Receptors, G-Protein-Coupled / drug effects*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, Neuropeptide / analysis*
  • Receptors, Neuropeptide / biosynthesis
  • Receptors, Neuropeptide / drug effects*
  • Receptors, Neuropeptide / genetics


  • Amino Acid Chloromethyl Ketones
  • Caspase Inhibitors
  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Neuropeptides
  • Orexin Receptors
  • Orexins
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Caspases