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  • Mitochondrial iron chelation as a novel anti-cancer strategy

    Author(s)
    Sandoval-Acuna, Cristian
    Tomkova, Veronika
    Cardenas, Natalia Torrealba
    Neuzil, Jiri
    Repkova, Krystina
    Stursa, Jan
    Werner, Lukas
    Truksa, Jaroslav
    Griffith University Author(s)
    Neuzil, Jiri
    Year published
    2018
    Metadata
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    Abstract
    Iron is an indispensable micronutrient required for function of key cellular enzymes required for DNA replication and repair, and for mitochondrial respiration and metabolism. Within cells, iron is primarily utilized in mitochondria, where it is essential for the synthesis of Fe-S clusters and heme. The role of iron in carcinogenesis is widely accepted, and tumor cells require higher amounts of iron for their survival and proliferation. Indeed, iron chelation has been proposed as an alternative strategy to target cancer cells. Therefore, we synthesized a mitochondrially targeted derivative of the iron chelator deferoxamine ...
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    Iron is an indispensable micronutrient required for function of key cellular enzymes required for DNA replication and repair, and for mitochondrial respiration and metabolism. Within cells, iron is primarily utilized in mitochondria, where it is essential for the synthesis of Fe-S clusters and heme. The role of iron in carcinogenesis is widely accepted, and tumor cells require higher amounts of iron for their survival and proliferation. Indeed, iron chelation has been proposed as an alternative strategy to target cancer cells. Therefore, we synthesized a mitochondrially targeted derivative of the iron chelator deferoxamine (mDFO) and evaluated its ability to eliminate cancer cells selectively. Our results show that mDFO is at least 100-fold more efficient than DFO in killing breast cancer cells. Moreover, mDFO was able to reduce mitochondrial respiration and aconitase activity, increase mitochondrial and cellular ROS production, and trigger the activation of mitophagy. Taken together, our data strongly support the role of mDFO as a novel and efficient compound in the selective elimination of cancer cells.
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    Conference Title
    Free Radical Biology and Medicine
    Volume
    120
    DOI
    https://doi.org/10.1016/j.freeradbiomed.2018.04.202
    Subject
    Medicinal and Biomolecular Chemistry
    Biochemistry and Cell Biology
    Medical Biochemistry and Metabolomics
    Science & Technology
    Life Sciences & Biomedicine
    Endocrinology & Metabolism
    Molecular Biology
    Publication URI
    http://hdl.handle.net/10072/402388
    Collection
    • Conference outputs

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