Learn More
Novel chemotherapeutics with marked and selective antitumor activity are essential to develop, particularly those that can overcome resistance to established therapies. Iron (Fe) is critical for cell-cycle progression and DNA synthesis and potentially represents a novel molecular target for the design of new anticancer agents. The aim of this study was to(More)
Numerous studies have suggested that iron (Fe) chelators such as desferrioxamine (DFO) may be useful antitumor agents (Blatt and Stitely, Cancer Res 47:1749, 1987; Becton and Bryles, Cancer Res 48:7189, 1988). Recent work with several analogues of the lipophilic Fe chelator, pyridoxal isonicotinoyl hydrazone (PIH), indicate that some of these ligands are(More)
Iron uptake by mammalian cells is mediated by the binding of serum Tf to the TfR. Transferrin is then internalized within an endocytotic vesicle by receptor-mediated endocytosis and the Fe released from the protein by a decrease in endosomal pH. Apart from this process, several cell types also have other efficient mechanisms of Fe uptake from Tf that(More)
Iron represents a paradox for living systems by being essential for a wide variety of metabolic processes (oxygen transport, electron transport, DNA synthesis, etc) but also having the potential to cause deleterious effects. Because of Iron's virtual insolubility and potential toxicity under physiological conditions, specialized molecules for the(More)
  • P Ponka
  • The American journal of the medical sciences
  • 1999
Heme is a complex of iron with protoporphyrin IX that is essential for the function of all aerobic cells. Heme serves as the prosthetic group of numerous hemoproteins (eg, hemoglobin, myoglobin, cytochromes, guanylate cyclase, and nitric oxide synthase) and plays an important role in controlling protein synthesis and cell differentiation. Cellular heme(More)
  • P Ponka
  • Kidney international. Supplement
  • 1999
Iron is essential for oxidation-reduction catalysis and bioenergetics, but unless appropriately shielded, iron plays a key role in the formation of toxic oxygen radicals that can attack all biological molecules. Hence, specialized molecules for the acquisition, transport (transferrin), and storage (ferritin) of iron in a soluble nontoxic form have evolved.(More)
From the Department of Pediatrics and the Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis (R.E.F.); and the Lady Davis Institute for Medical Research, Jewish General Hospital, and the Departments of Physiology and Medicine, McGill University — both in Montreal (P.P.). Address reprint(More)
The mitochondrion is well known for its key role in energy transduction. However, it is less well appreciated that it is also a focal point of iron metabolism. Iron is needed not only for heme and iron sulfur cluster (ISC)-containing proteins involved in electron transport and oxidative phosphorylation, but also for a wide variety of cytoplasmic and nuclear(More)
Cytosolic ferritin sequesters and stores iron and, consequently, protects cells against iron-mediated free radical damage. However, the function of the newly discovered mitochondrial ferritin (MtFt) is unknown. To examine the role of MtFt in cellular iron metabolism, we established a cell line that stably overexpresses mouse MtFt under the control of a(More)