Journal article
Treatment of Pancreatic Cancer with Pharmacological Ascorbate
Current pharmaceutical biotechnology, Vol.16(9), pp.759-770
2015
DOI: 10.2174/138920101609150715135921
PMCID: PMC4895694
PMID: 26201606
Abstract
The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that high-dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs. normal cells, suggesting a promising new role of ascorbate as a therapeutic agent. At physiologic concentrations, ascorbate functions as a reducing agent and antioxidant. However, when pharmacological ascorbate is given intravenously, it is possible to achieve millimolar plasma concentration. At these pharmacological levels, and in the presence of catalytic metal ions, ascorbate can induce oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in vitro and in vivo studies have demonstrated ascorbate oxidation occurs extracellularly, generating H2O2 flux into cells resulting in oxidative stress. Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts and displays synergistic cytotoxic effects when combined with gemcitabine in pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic cancer patients have demonstrated safety and potential efficacy. In this chapter, we will review the mechanism of ascorbate-induced cytotoxicity, examine the use of pharmacological ascorbate in treatment and assess the current data supporting its potential as an adjuvant in pancreatic cancer.
Details
- Title: Subtitle
- Treatment of Pancreatic Cancer with Pharmacological Ascorbate
- Creators
- John A CieslakJoseph J Cullen - 1528 JCP, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. joseph-cullen@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Current pharmaceutical biotechnology, Vol.16(9), pp.759-770
- DOI
- 10.2174/138920101609150715135921
- PMID
- 26201606
- PMCID
- PMC4895694
- NLM abbreviation
- Curr Pharm Biotechnol
- ISSN
- 1389-2010
- eISSN
- 1873-4316
- Publisher
- Netherlands
- Grant note
- T32 CA148062 / NCI NIH HHS P42 ES013661 / NIEHS NIH HHS U01166800 / PHS HHS I01 BX001318 / BLRD VA R01 CA184051 / NCI NIH HHS CA111365 / NCI NIH HHS R01 CA111365 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA169046 / NCI NIH HHS
- Language
- English
- Date published
- 2015
- Academic Unit
- Surgery; Radiation Oncology
- Record Identifier
- 9984051710102771
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