Journal article
Pharmacological ascorbate inhibits pancreatic cancer metastases via a peroxide-mediated mechanism
Scientific reports, Vol.10(1), pp.17649-17649
10/19/2020
DOI: 10.1038/s41598-020-74806-2
PMCID: PMC7572461
PMID: 33077776
Abstract
Pharmacological ascorbate (P-AscH(-), high-dose, intravenous vitamin C) is cytotoxic to tumor cells in doses achievable in humans. Phase I studies in pancreatic cancer (PDAC) utilizing P-AscH(-) have demonstrated increases in progression free survival, suggesting a reduction in metastatic disease burden. The purpose of this study was to determine the effects of P-AscH(-) on metastatic PDAC. Several in vitro and in vivo mechanisms involved in PDAC metastases were investigated following treatment with P-AscH(-). Serum from PDAC patients in clinical trials with P-AscH(-) were tested for the presence and quantity of circulating tumor cell-derived nucleases. P-AscH(-) inhibited invasion, basement membrane degradation, decreased matrix metalloproteinase expression, as well as clonogenic survival and viability during exposure to fluid shear stress. In vivo, P-AscH(-) significantly decreased formation of ascites, tumor burden over time, circulating tumor cells, and hepatic metastases. Both in vitro and in vivo findings were reversed with the addition of catalase suggesting that the effect of P-AscH(-) on metastatic disease is mediated by hydrogen peroxide. Finally, P-AscH(-) decreased CTC-derived nucleases in subjects with stage IV PDAC in a phase I clinical trial. We conclude that P-AscH(-) attenuates the metastatic potential of PDAC and may prove to be effective for treating advanced disease.
Details
- Title: Subtitle
- Pharmacological ascorbate inhibits pancreatic cancer metastases via a peroxide-mediated mechanism
- Creators
- Brianne R. O'Leary - University of IowaMatthew S. Alexander - Roy J. and Lucille A. Carver College of MedicineJuan Du - University of IowaDevon L. Moose - University of IowaMichael D. Henry - University of IowaJoseph J. Cullen - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.10(1), pp.17649-17649
- DOI
- 10.1038/s41598-020-74806-2
- PMID
- 33077776
- PMCID
- PMC7572461
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- P01 CA217797; CA169046; CA148062; P30CA086862; T32 GM0677954 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 10/19/2020
- Academic Unit
- Molecular Physiology and Biophysics; Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984313088802771
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