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; Silvio Aime

doi:10.18632/oncotarget.25416

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

Applied Medicine

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

4 Downloads (Pure)

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 language	English
Pages (from-to)	27974-27984
Number of pages	11
Journal	Oncotarget
Volume	9
Issue number	46
DOIs	https://doi.org/10.18632/oncotarget.25416
Publication status	Published - 15 Jun 2018

Bibliographical note

This research was funded by MIUR (PRIN 2012 code 2012SK7ASN). SA and SGC acknowledge the European Union’s Horizon 2020 research and innovation programme under grant agreement No 668119 (project “IDentIFY”), SC the postdoctoral grant by Fondazione Cassa di Risparmio di Firenze (n°2013.0494) provided by FiorGen.

Keywords

Cancer therapy
Ferritin
HeLa cells
Iron release
TFR1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.25416Licence: CC BY

Cutrin_etal_Oncotarget_Cancer_cell_death_VOR
https://creativecommons.org/licenses/by/3.0/
Final published version, 2.74 MBLicence: CC BY

Cite this

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title = "Cancer cell death induced by ferritins and the peculiar role of their labile iron pool",

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.",

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note = "This research was funded by MIUR (PRIN 2012 code 2012SK7ASN). SA and SGC acknowledge the European Union{\textquoteright}s Horizon 2020 research and innovation programme under grant agreement No 668119 (project “IDentIFY”), SC the postdoctoral grant by Fondazione Cassa di Risparmio di Firenze (n°2013.0494) provided by FiorGen. ",

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AU - Cutrin, Juan Carlos

AU - Alberti, Diego

AU - Bernacchioni, Caterina

AU - Ciambellotti, Silvia

AU - Turano, Paola

AU - Luchinat, Claudio

AU - Crich, Simonetta Geninatti

AU - Aime, Silvio

N1 - This research was funded by MIUR (PRIN 2012 code 2012SK7ASN). SA and SGC acknowledge the European Union’s Horizon 2020 research and innovation programme under grant agreement No 668119 (project “IDentIFY”), SC the postdoctoral grant by Fondazione Cassa di Risparmio di Firenze (n°2013.0494) provided by FiorGen.

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

UN SDGs

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Cite this

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

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BD Calibur

Cite this