Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice

Area of Science:

• Biochemistry
• Oncology
• Pharmacology

Background:

• Ascorbic acid (vitamin C) is typically known as an antioxidant.
• Its role at pharmacologic concentrations in cancer treatment is under investigation.

Purpose of the Study:

• To investigate the prooxidant effects of pharmacologic ascorbic acid concentrations.
• To evaluate the efficacy of ascorbic acid in reducing tumor growth in vivo.

Main Methods:

• In vitro cytotoxicity assays on various cancer cell lines.
• In vivo studies using mice with glioblastoma xenografts and other established tumors.
• Real-time microdialysis to measure ascorbate radical and hydrogen peroxide levels in tumor interstitial fluid and blood.

Main Results:

• Pharmacologic ascorbic acid demonstrated selective prooxidant and cytotoxic effects on cancer cells in vitro.
• In vivo, a single dose of ascorbic acid led to sustained hydrogen peroxide formation within tumors but not blood.
• Daily administration of pharmacologic ascorbic acid significantly inhibited the growth of ovarian, pancreatic, and glioblastoma tumors in mice.

Conclusions:

• Ascorbic acid at pharmacologic concentrations functions as a prooxidant, selectively targeting cancer cells.
• Intravenous administration of ascorbic acid achieves therapeutic concentrations in humans.
• Ascorbic acid shows potential as a prodrug therapy for cancers with poor prognosis.