Cancer cell death induced by ferritins and the peculiar role of their labile iron pool
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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
Simonetta Geninatti Crich, email: [email protected]
Claudio Luchinat, email: [email protected]
Keywords: ferritin; iron release; cancer therapy; HeLa cells; TFR1
Received: May 04, 2017 Accepted: April 28, 2018 Published: June 15, 2018
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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