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

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. +10 more·2015·Cancer Research

Published version of a preprint

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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  • Giving ascorbate by injection does not block the effects of chemotherapy or radiotherapy.

    “Numerous preclinical and clinical studies indicate that parenteral injection of pharmacological ascorbate does not interfere with chemotherapy or radiotherapy and may even act synergistically43,104,105.”

    From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [105]

  • Giving ascorbate by injection may act synergistically with chemotherapy or radiotherapy.

    “Numerous preclinical and clinical studies indicate that parenteral injection of pharmacological ascorbate does not interfere with chemotherapy or radiotherapy and may even act synergistically43,104,105.”

    From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [105]

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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)
Venue
Cancer Research
Published
2015-08-13
Volume
75
Issue
16
Pages
3314-3326
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
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
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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