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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.

SUBMITTER: Cutrin JC

PROVIDER: S-EPMC6021343 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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

Cutrin Juan Carlos JC Alberti Diego D Bernacchioni Caterina C Ciambellotti Silvia S Turano Paola P Luchinat Claudio C Crich Simonetta Geninatti SG Aime Silvio S

Oncotarget 20180615 46

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 o ...[more]

PMID: 29963255

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