Drug Developers Eye Cancer Iron Storage Proteins

Investigators from the German Cancer Research Center (DFKZ; Heidelberg, Germany) reported in the March 15, 2009, edition of the journal Cancer Research that inhibition of active NF-kappa-B triggered down-regulation of FHCs, which caused an increase of free intracellular iron. This increase induced massive generation of ROS. Direct downregulation of FHCs by siRNA caused ROS-dependent cell death, while in a different model system high concentrations of ROS induced cell death of malignant T cells.

T cells isolated from healthy donors did not display downregulation of FHCs, and therefore, did not show an increase in iron and cell death upon NF-kappa-B inhibition. In addition, in a mouse T cell lymphoma model, the inhibition of NF-kappa-B and subsequent down-regulation of FHCs significantly delayed tumor growth.

Based on these findings, the investigators concluded that, "Our results promote FHC as a potential target for effective therapy in lymphomas with aberrant NF-kappa-B signaling.”

Related Links:
German Cancer Research Center