Journal article
Pharmacological ascorbate and ionizing radiation (IR) increase labile iron in pancreatic cancer
Redox biology, Vol.2(1), pp.22-27
2013
DOI: 10.1016/j.redox.2013.11.005
PMCID: PMC3881203
PMID: 24396727
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.
Details
- Title: Subtitle
- Pharmacological ascorbate and ionizing radiation (IR) increase labile iron in pancreatic cancer
- Creators
- Justin C Moser - Free Radical and Radiation Biology Program and ESR Facility, Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USAMalvika Rawal - Free Radical and Radiation Biology Program and ESR Facility, Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USABrett A Wagner - Free Radical and Radiation Biology Program and ESR Facility, Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USAJuan Du - Free Radical and Radiation Biology Program and ESR Facility, Department of Radiation Oncology, The University of Iowa, Iowa City, IA, USAJoseph J Cullen - 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, USAGarry R Buettner - 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
- Resource Type
- Journal article
- Publication Details
- Redox biology, Vol.2(1), pp.22-27
- DOI
- 10.1016/j.redox.2013.11.005
- PMID
- 24396727
- PMCID
- PMC3881203
- NLM abbreviation
- Redox Biol
- ISSN
- 2213-2317
- eISSN
- 2213-2317
- Publisher
- Netherlands
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01 GM073929 / NIGMS NIH HHS I01 BX001318 / BLRD VA R01 CA 169046 / NCI NIH HHS U01 CA166800 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA169046 / NCI NIH HHS
- Language
- English
- Date published
- 2013
- Academic Unit
- Surgery; Radiation Oncology
- Record Identifier
- 9984047669102771
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