Treatment of Pancreatic Cancer with Pharmacological Ascorbate

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.

John A. Cieslak and Joseph J. Cullen*
Free Radical and Radiation Biology Program, Departments of Surgery and Radiation Oncology,Holden Comprehensive Cancer Center, The University of Iowa Hospitals and Clinics and the University of Iowa College of Medicine, Iowa City, IA 52242, USA

You May Also Like