In both cases, the activity of the drugs is associated with the presence of iron. Iron is present in large excess bound to hemoglobin in erythrocytes, where the Plasmodia parasites are located. The active moiety of artemisinin-like drugs is an endoperoxide bridge, whose reductive homolysis is promoted by iron -heme leading to C4-centered alkylating radicals. These radical molecules cause macromolecular damage by alkylating essential malarial LY2835219 proteins inducing cell death of parasites. On the other hand, iron content is higher in tumor cells than in normal cells making them more susceptible to artemisinins. We and others have shown that the susceptibility of tumor cells to artemisinins can further be enhanced by the addition of transferrin or ferrous iron. The role of artemisinins and iron for malaria treatment has been intensively investigated during the past years, whereas the role of iron for tumor treatment with artemisinins is far less understood. The iron-binding protein, transferrin, is internalized into cancer cells after binding to the transferrin receptor. This is a transmembrane glycoprotein involved in iron uptake by internalization of transferrin. TfR exerts growth regulatory functions and is over-expressed in rapidly growing tumors. The expression of TfR is of prognostic significance for several tumor types. Ferrous iron can either be bound to transferrin or to other proteins before uptake. The ATP-binding cassette transporters ABCB6 and ABCB7 are involved in iron homeostasis. They are located in the mitochondria and transport heme and protoporphyrins into these organelles. Most ABC transporters are involved in the active transport of phospholipids, ions, peptides, steroids, polysaccharides, amino acids, bile acids, pharmaceutical drugs and other xenobiotic compounds. In humans, 49 different ABC transporters have been identified, which are classified into seven sub-families. In healthy organs several ABC transporters protect against the harmful effects of xenobiotics taken up with food. A high expression can, therefore, be found in the gastrointestinal tract, liver, and kidney. A protective function is also given as components of the blood brain barrier and the blood placenta barrier. A modified propidium iodide assay was used to assess the compound��s activity in Oncotest��s 36 cell line panel. Briefly, cells were harvested from exponential phase cultures by trypsinization, counted and plated in 96 well flat-bottomed micro-titer plates at a cell density depending on the cell line. After a 24 h recovery period to allow the cells to adhere and resume exponential growth, 10 ml of culture medium or of culture medium containing the test compounds were added to the cells. The compounds were applied in triplicates at five concentrations. Following four days of continuous drug GDC-0879 exposure, medium or medium with test compound, including all dead cells suspended in the culture medium, was aspirated and replaced by 200 ml of an aqueous propidium iodide solution. To measure the amount of living cells, cells were permeabilized by freezing the plates, resulting in the death of all cells that had remained attached to the bottom of the well after the incubation period.