title: Ammonium ions improve the survival of glutamine-starved hybridoma cells.
abstract: BACKGROUND
  As a consequence of a reprogrammed metabolism, cancer cells are dependent on the amino acid l-glutamine for their survival, a phenomenon that currently forms the basis for the generation of new, cancer-specific therapies. In this paper, we report on the role which ammonium ions, a product of glutaminolysis, play on the survival of l-glutamine-deprived Sp2/0-Ag14 mouse hybridoma cells.
  
  
  RESULTS
  The supplementation of l-glutamine-starved Sp2/0-Ag14 cell cultures with either ammonium acetate or ammonium chloride resulted in a significant increase in viability. This effect did not depend on the ability of cells to synthesize l-glutamine, and was not affected by the co-supplementation with α-ketoglutarate. When we examined the effect of ammonium acetate and ammonium chloride on the induction of apoptosis by glutamine deprivation, we found that ammonium salts did not prevent caspase-3 activation or cytochrome c leakage, indicating that they did not act by modulating core apoptotic processes. However, both ammonium acetate and ammonium chloride caused a significant reduction in the number of l-glutamine-starved cells exhibiting apoptotic nuclear fragmentation and/or condensation.
  
  
  CONCLUSIONS
  All together, our results show that ammonium ions promote the survival of l-glutamine-deprived Sp2/0-Ag14 cells and modulate late-apoptotic events. These findings highlight the complexity of the modulation of cell survival by l-glutamine, and suggest that targeting survival-signaling pathways modulated by ammonium ions should be examined as a potential anti-cancer strategy.
authors.affiliation: Biomolecular Sciences, Laurentian University, Sudbury, ON P3E 2C6 Canada.
authors.forename: Abdelmuhsen
authors.initials: A
authors.lastname: Abusneina
authors.affiliation: Biomolecular Sciences, Laurentian University, Sudbury, ON P3E 2C6 Canada ; Department of Chemistry and Biochemistry, Laurentian University, Sudbury, ON P3E 2C6 Canada ; Department of Biology, Laurentian University, Sudbury, ON P3E 2C6 Canada.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gauthier
keywords: Ammonium; Apoptosis; Caspase; Glutamine; Glutaminolysis; Hybridoma