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Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer
Open accessPublished 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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“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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“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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Metadata
- 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
- Venue
- Cancer Research
- Published
- 2015-08-13
- Volume
- 75
- Issue
- 16
- Pages
- 3314-3326
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- 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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