title: Transferrin ensures survival of ovarian carcinoma cells when apoptosis is induced by TNFalpha, FasL, TRAIL, or Myc.
abstract: The activation of Myc induces apoptosis of human ovarian adenocarcinoma N.1 cells when serum factors are limited. However, the downstream mechanism that is triggered by Myc is unknown. Myc-activation and treatment with the proapoptotic ligands TNFalpha, FasL, and TRAIL induced H-ferritin expression under serum-deprived conditions. H-ferritin chelates intracellular iron and also intracellular iron sequestration by deferoxamine-induced apoptosis of N.1 cells. Supplementation of serum-free medium with holo-transferrin blocked apoptosis of N.1 cells that was induced by Myc-activation or by treatment with TNFalpha, FasL, and TRAIL, whereas apotransferrin did not prevent apoptosis. This suggests that intracellular iron depletion was a trigger for apoptosis and that transferrin-bound iron rescued N.1 cells. Furthermore, apoptosis of primary human ovarian carcinoma cells, which was induced by TNFalpha, FasL, and TRAIL, was also inhibited by holo-transferrin. The data suggest that Myc-activation, FasL, TNFalpha, and TRAIL disturbed cellular iron homeostasis, which triggered apoptosis of ovarian carcinoma cells and that transferrin iron ensured survival by re-establishing this homeostasis.
authors: Institute of Clinical Pathology, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors: Sandra
authors: S
authors: Fassl
authors: Christina
authors: C
authors: Leisser
authors: Simone
authors: S
authors: Huettenbrenner
authors: Susanne
authors: S
authors: Maier
authors: Georg
authors: G
authors: Rosenberger
authors: Stephan
authors: S
authors: Strasser
authors: Michael
authors: M
authors: Grusch
authors: Gerhard
authors: G
authors: Fuhrmann
authors: Katharina
authors: K
authors: Leuhuber
authors: Doris
authors: D
authors: Polgar
authors: Josefine
authors: J
authors: Stani
authors: Brigitte
authors: B
authors: Tichy
authors: Christine
authors: C
authors: Nowotny
authors: Georg
authors: G
authors: Krupitza
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002470:Cell Survival / Q000502:physiology*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014168:Transferrin / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016271:Proto-Oncogene Proteins c-myc; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014168:Transferrin; D014409:Tumor Necrosis Factor-alpha