Oncotarget

Research Papers:

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 _ and Silvio Aime

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Oncotarget. 2018; 9:27974-27984. https://doi.org/10.18632/oncotarget.25416

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Abstract

Juan Carlos Cutrin1, Diego Alberti1, Caterina Bernacchioni2, Silvia Ciambellotti2, Paola Turano2, Claudio Luchinat2, Simonetta Geninatti Crich1 and Silvio Aime2,3

1University of Torino, Department of Molecular Biotechnology and Health Sciences, Torino, Italy

2Center for Magnetic Resonance, University of Florence, Florence, Italy

3IBB-CNR, Sede Secondaria c/o MBC, Torino, Italy

Correspondence to:

Simonetta Geninatti Crich, email: simonetta.geninatti@unito.it

Claudio Luchinat, email: luchinat@cerm.unifi.it

Keywords: ferritin; iron release; cancer therapy; HeLa cells; TFR1

Received: May 04, 2017     Accepted: April 28, 2018     Published: June 15, 2018

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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