Cited by 112Vitamin C and Antioxidants ResearchEffects of Radiation ExposurePancreatic and Hepatic Oncology Research

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Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer

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Du, Juan, Cieslak, John A., Welsh, Jessemae L., Sibenaller, Zita A., Allen, Bryan G., Wagner, Brett A., Kalen, Amanda L., Doskey, Claire M., Strother, Robert K., Button, Anna M., Mott, Sarah L., Smith, Brian, Tsai, Susan, Mezhir, James, Goswami, Prabhat C., Spitz, Douglas R., Buettner, Garry R., Cullen, Joseph J.·2015·Cancer Research

DOI 10.1158/0008-5472.can-14-1707PMC PMC4537815

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Abstract

The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Because pancreatic cancer cells are sensitive to H2O2 generated by ascorbate, they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacologic ascorbate enhances the cytotoxic effects of ionizing radiation as seen by decreased cell viability and clonogenic survival in all pancreatic cancer cell lines examined, but not in nontumorigenic pancreatic ductal epithelial cells. Ascorbate radiosensitization was associated with an increase in oxidative stress–induced DNA damage, which was reversed by catalase. In mice with established heterotopic and orthotopic pancreatic tumor xenografts, pharmacologic ascorbate combined with ionizing radiation decreased tumor growth and increased survival, without damaging the gastrointestinal tract or increasing systemic changes in parameters indicative of oxidative stress. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer. Cancer Res; 75(16); 3314–26. ©2015 AACR.

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Authors: Du, J., Cieslak, J. A., Welsh, J. L., Sibenaller, Z. A., Allen, B. G., Wagner, B. A., Kalen, A. L., Doskey, C. M., Strother, R. K., Button, A. M., Mott, S. L., Smith, B., Tsai, S., Mezhir, J., Goswami, P. C., Spitz, D. R., Buettner, G. R., & Cullen, J. J.
Affiliations: University of Iowa (US)
University of Iowa Holden Comprehensive Cancer Center (US)
Medical College of Wisconsin (US)
ORCID: Du, Juan
Cieslak, John A.
Sibenaller, Zita A.
Allen, Bryan G.
Wagner, Brett A.
Strother, Robert K.
Button, Anna M.
Mott, Sarah L.
Tsai, Susan
Goswami, Prabhat C.
Spitz, Douglas R.
Buettner, Garry R.
Cullen, Joseph J.
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2015-08-13
Volume: 75
Issue: 16
Pages: 3314-3326
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-14-1707
PMC: PMC4537815
OpenAlex: W2106438648
Cited by: 112
References: 52
Citations by year: 2026: 5 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 13 · 2021: 12 · 2020: 9 · 2019: 7 · 2018: 18 · 2017: 18 · 2016: 3 · 2015: 2
FWCI: 13.16
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Veterans Affairs (I01 BX001318)
National Institutes of Health (4r01ca111365-10)
National Heart, Lung, and Blood Institute (T35HL007485)
National Cancer Institute (R01 CA-111365, R01CA182804, T32CA148062, R01CA169046, R01CA184051, T32CA078586, P30CA086862)
National Institute of Environmental Health Sciences (P42ES013661, P30ES005605)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords: pharmacologic ascorbate, vitamin C, radiosensitization, pancreatic cancer, ionizing radiation, hydrogen peroxide, oxidative stress, DNA damage, catalase, clonogenic survival, tumor xenografts, combination therapy
MeSH terms: Animals, Antioxidants, Ascorbic Acid, Cell Line, Cell Survival, DNA Damage, Dose-Response Relationship, Radiation, Glutathione, Humans, Hydrogen Peroxide, Mice, Nude, Pancreatic Neoplasms, Radiation-Sensitizing Agents, Radiation, Ionizing, Linear Models, Oxidative Stress, Glutathione Disulfide, Xenograft Model Antitumor Assays, Cell Line, Tumor, Tumor Burden, Kaplan-Meier Estimate, Chemoradiotherapy

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