Iron Induces Death in Tumor Cells
Tumor cells and healthy cells differ considerably in metabolism intensity. Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have taken advantage of this difference: By releasing cellular iron they were able to induce death selectively in tumor cells.
Rapid growth of cancer cells and their frequent divisions have their price: Cancer cells need considerably more energy than healthy cells. Their metabolism runs at full speed and requires large amounts of micronutrients, particularly iron. However, high levels of iron in the cell lead to the production of extremely harmful free radicals. To protect itself from these, the cell inactivates free iron by binding it to what are called iron storage proteins.
Collaborating with physicians of the Dermatology Department of Mannheim University Hospitals, Dr. Karsten Gülow and Professor Dr. Peter Krammer, head of the Division of Immunogenetics at DKFZ, investigated Sézary’s disease (also called Sézary syndrome), an extremely aggressive type of cutaneous T cell lymphoma. The majority of currently available treatments are not really effective against this fatal type of cancer.
Using a molecular-biological trick, Gülow and colleagues succeeded in blocking the production of one of the iron storage proteins in lymphoma cells. This leads to a rise in the level of free, non-bound iron in these cells. The iron boosts the production of free oxygen radicals which cause oxidative stress and, thus, cause damage to the cancer cells and induce their death. Healthy cells with their low iron level, however, survive the treatment unharmed.
The DKFZ researchers have already found evidence that this iron effect also works in other lymphomas. They are now investigating whether selective release of iron may be a suitable approach for developing a novel cancer treatment.
Michael K. Kiessling, Claus D. Klemke, Marcin M. Kamiñski, Ioanna E. Galani, Peter H. Krammer, and Karsten Gülow: Inhibition of constitutively activated NF-κB induces ROS- and iron dependent cell death in cutaneous T cell lymphoma. Cancer Research 2009; DOI:10.1158/0008-5472.CAN-08-3221
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.