|
|||||
|
|
DMT1 Inhibitors Kill Cancer Stem Cells by Blocking Lysosomal Iron Translocation |
|
| Authors: | Andreea L Turcu Antoine Versini Nadjib Khene Christine Gaillet Dr Tatiana Cañeque Dr Sebastian Müller Dr Raphaël Rodriguez |
| Institution: | 1. Laboratori de Química Farmacèutica (Unitat Associada al CSIC), Facultat de Farmàcia i Ciències de l'Alimentació i Institut de Biomedicina, University of Barcelona, Av. Joan XXIII 27–31, 08028 Barcelona, Spain;2. Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France;3. Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France
PSL Université, 60 rue Mazarine, 75006 Paris, France Chemical Biology of Cancer Laboratory, CNRS UMR 3666, INSERM U1143, 75248 Paris Cedex 05, France |
| Abstract: | Cancer stem cells (CSC) constitute a cell subpopulation in solid tumors that is responsible for resistance to conventional chemotherapy, metastasis and cancer relapse. The natural product Salinomycin can selectively target this cell niche by directly interacting with lysosomal iron, taking advantage of upregulated iron homeostasis in CSC. Here, inhibitors of the divalent metal transporter 1 (DMT1) have been identified that selectively target CSC by blocking lysosomal iron translocation. This leads to lysosomal iron accumulation, production of reactive oxygen species and cell death with features of ferroptosis. DMT1 inhibitors selectively target CSC in primary cancer cells and circulating tumor cells, demonstrating the physiological relevance of this strategy. Taken together, this opens up opportunities to tackle unmet needs in anti-cancer therapy. |
| Keywords: | bioinorganic chemistry cancer iron oxygen stem cells |