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.
Bibliographical noteThis 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.
- Cancer therapy
- HeLa cells
- Iron release