Cancer cell death induced by ferritins and the peculiar role of their labile iron pool

Juan Carlos Cutrin, Diego Alberti, Caterina Bernacchioni, Silvia Ciambellotti, Paola Turano, Claudio Luchinat, Simonetta Geninatti Crich* (Corresponding Author), Silvio Aime

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cellular uptake of human H-ferritin loaded with 50 or 350 iron ions results in significant cytotoxicity on HeLa cells at submicromolar concentrations. Conversely, Horse Spleen Ferritin, that can be considered a model of L-cages, as it contains only about 10% of H subunits, even when loaded with 1000 iron ions, is toxic only at >1 order of magnitude higher protein concentrations. We propose here that the different cytotoxicity of the two ferritin cages originates from the presence in H-ferritin of a pool of non-biomineralized iron ions bound at the ferroxidase catalytic sites of H-ferritin subunits. This iron pool is readily released during the endosomal-mediated H-ferritin internalization.

Original languageEnglish
Pages (from-to)27974-27984
Number of pages11
JournalOncotarget
Volume9
Issue number46
DOIs
Publication statusPublished - 15 Jun 2018

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Keywords

  • Cancer therapy
  • Ferritin
  • HeLa cells
  • Iron release
  • TFR1

ASJC Scopus subject areas

  • Oncology

Cite this

Cutrin, J. C., Alberti, D., Bernacchioni, C., Ciambellotti, S., Turano, P., Luchinat, C., Crich, S. G., & Aime, S. (2018). Cancer cell death induced by ferritins and the peculiar role of their labile iron pool. Oncotarget, 9(46), 27974-27984. https://doi.org/10.18632/oncotarget.25416