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)
Year published
2018
Metadata
Show full item recordAbstract
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 ...
View more >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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View more >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.
View less >
Conference Title
Free Radical Biology and Medicine
Volume
120
Subject
Medicinal and biomolecular chemistry
Biochemistry and cell biology
Medical biochemistry and metabolomics
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Molecular Biology