Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro and animal xenograft experiments with human pharmacokinetic reference data.
PubMed 18678913 · doi:10.1073/pnas.0804226105
What was done
The authors tested the prooxidant, hydrogen-peroxide-dependent cytotoxic effects of pharmacologic ascorbate concentrations across cancer cell lines in vitro. In mice bearing glioblastoma xenografts, they used real-time microdialysis to measure ascorbate radical and hydrogen peroxide generation in blood versus tumor interstitial fluid after parenteral administration. They evaluated the effect of daily parenteral pharmacologic ascorbate on the growth rates of ovarian, pancreatic, and glioblastoma tumor xenografts in mice, and compared mouse exposure levels to human intravenous pharmacokinetics.
What was found
Parenteral ascorbate produced sustained ascorbate radical and hydrogen peroxide formation selectively within tumor interstitial fluid rather than blood. Daily pharmacologic ascorbate significantly reduced tumor growth rates in mouse xenograft models of ovarian cancer (P < 0.005), pancreatic cancer (P < 0.05), and glioblastoma (P < 0.001). The abstract reports that comparable concentrations were achieved in humans receiving intravenous ascorbate, but no specific human clinical outcome numbers or sample sizes are provided.
Why it matters
The study outlines a mechanism whereby high-dose parenteral ascorbate functions as a prooxidant prodrug generating localized hydrogen peroxide in tumors, providing a biological rationale for testing intravenous ascorbate in aggressive human cancers.
Limits
The therapeutic efficacy findings are strictly from cell cultures and mouse xenograft models, which cannot establish clinical efficacy or safety in human cancer patients. The abstract does not disclose animal sample sizes, human cohort size, precise dosing, quantitative tumor volumes, or survival metrics.
Cited by
- supports Intravenous doses of vitamin C greater than 1 gram generate hydrogen peroxide, whereas physiological concentrations around 50 micromolar act primarily as an antioxidant.