title: Pharmacological ascorbate and ionizing radiation (IR) increase labile iron in pancreatic cancer.
abstract: Labile iron, i.e. iron that is weakly bound and is relatively unrestricted in its redox activity, has been implicated in both the pathogenesis as well as treatment of cancer. Two cancer treatments where labile iron may contribute to their mechanism of action are pharmacological ascorbate and ionizing radiation (IR). Pharmacological ascorbate has been shown to have tumor-specific toxic effects due to the formation of hydrogen peroxide. By catalyzing the oxidation of ascorbate, labile iron can enhance the rate of formation of hydrogen peroxide; labile iron can also react with hydrogen peroxide. Here we have investigated the magnitude of the labile iron pool in tumor and normal tissue. We also examined the ability of pharmacological ascorbate and IR to change the size of the labile iron pool. Although a significant amount of labile iron was seen in tumors (MIA PaCa-2 cells in athymic nude mice), higher levels were seen in murine tissues that were not susceptible to pharmacological ascorbate. Pharmacological ascorbate and irradiation were shown to increase the labile iron in tumor homogenates from this murine model of pancreatic cancer. As both IR and pharmacological ascorbate may rely on labile iron for their effects on tumor tissues, our data suggest that pharmacological ascorbate could be used as a radio-sensitizing agent for some radio-resistant tumors.
authors.affiliation: Free Radical and Radiation Biology Program and ESR Facility, Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USA.
authors.forename: Justin C
authors.initials: JC
authors.lastname: Moser
authors.affiliation: Free Radical and Radiation Biology Program and ESR Facility, Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USA.
authors.forename: Malvika
authors.initials: M
authors.lastname: Rawal
authors.affiliation: Free Radical and Radiation Biology Program and ESR Facility, Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USA.
authors.forename: Brett A
authors.initials: BA
authors.lastname: Wagner
authors.affiliation: Free Radical and Radiation Biology Program and ESR Facility, Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Free Radical and Radiation Biology Program and ESR Facility, Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USA ; Department of Surgery, The University of Iowa, Iowa City, IA, USA ; Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Cullen
authors.affiliation: Free Radical and Radiation Biology Program and ESR Facility, Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USA ; Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA, USA.
authors.forename: Garry R
authors.initials: GR
authors.lastname: Buettner
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011839:Radiation, Ionizing; D014183:Transplantation, Heterologous
chemical_list: D005293:Ferritins; D007501:Iron; D001205:Ascorbic Acid
keywords: Ascorbate; DFO, deferrioxamine or Desferal®; EPR; EPR, electron paramagnetic resonance; Electron paramagnetic resonance; Ferritin; IR, ionizing radiation; Ionizing radiation; LIP, labile iron pool; Labile iron; PBS, phosphate-buffered saline