Popular Science: Is iron the new star in cancer treatment?
Iron, one of the most important chemical elements, is indispensable to almost all forms of life. It is involved in essential cycles such as cell respiration and metabolism, replication of DNA, and repair of genetical material. A lack of iron causes multiple enzymes necessary for correct functioning of cells to malfunction; insufficient iron levels can also lead to the arrest of cell respiration, which thus undermines the growth and thriving of the affected cell.
Treating cancer through the use of substances that capture iron has been previously researched. The problem was that, usually, those substances caused an iron deficiency for the whole organism which caused adverse effects even to healthy cells. Deferoxamine is widely used for treating iron surplus by capturing iron atoms into its structure. This mechanism has become the foundation of a new approach to cancer treatment – targeting deferoxamine to mitochondria (energetic and respirational centre of the cell) of cancer cells using a chemical modification. This way mitochondria-targeted deferoxamine (mitoDFO) is created. It targets only the necessary parts of cells – mitochondria – and owing to an increased need for iron in cancer cells, it can therefore target those cells preferentially.
The main effect of this compound is targeted capturing of iron, as stated above. As such, it can arrest the growth of cancer cells, as well as of whole carcinomas in vitro. This compound also significantly limits the ability of cancer cells to spread through the body. MitoDFO was able to fully stop cellular respiration in under one hour in all tested cell lines. The application also increased the production of toxic reactive oxygen species (ROS) which can damage genetic material and proteins and thus cause cell death. To confirm this finding, antioxidants, which inhibit ROS, were applied and the antiproliferative effect was significantly decreased.
High mortality of cancer is linked to its ability to metastasize – spread through the whole organism and attack various tissues. In collaboration with Prof. Brábek from the Faculty of Science at Charles University, scientists tested the ability of mitoDFO to prevent the formation of metastasis. Research conducted on mouse breast cancer spreading to lungs has exhibited significant limitations of mobility of cancer cells in the body, hence preventing metastasis from forming. The formation of metastasis in lungs was almost completely inhibited.
In all experiments, mitoDFO was compared with pure deferoxamine, which was always less effective. These findings thus demonstrate the efficacy of the modified compound targeting only the needed parts of the cell – mitochondria. MitoDFO could become the base of new cancer treatment research concentrating on highly efficient drugs with low toxicity for healthy cells which would limit the adverse effects of treatments currently used.
The new drug has been developed with help from SmartBrain s.r.o. company, and it has been patented.
Sandoval-Acuña C, Torrealba N, Tomkova V, Jadhav SB, Blazkova K, Merta L, Lettlova S, Adamcová MK, Rosel D, Brábek J, Neuzil J, Stursa J, Werner L, Truksa J. Targeting Mitochondrial Iron Metabolism Suppresses Tumor Growth and Metastasis by Inducing Mitochondrial Dysfunction and Mitophagy. Cancer Res. 2021 May 1; 81 (9): 2289–2303; doi: 10.1158/0008-5472.CAN-20-1628. Epub 2021 Mar 8. PMID: 33685989