By Patrick Yang ’20

Ascorbate, or vitamin C, is a potential anti-cancer agent when paired with chemotherapy. Scientists hypothesize that ascorbate’s curative powers stem from its ability to produce hydrogen peroxide, which reduces iron to form free radicals – highly reactive molecules that damage DNA and cause cell death. Since aggressive cancers have unusually large intracellular iron pools that support cancer spread and growth, ascorbate might have the ability to exclusively target cancer cells while remaining nontoxic to normal cells. But because ascorbate therapy is a relatively new discovery that uses 800 to 1,000 times the daily recommended dosage of ascorbate, its safety and selectivity must still be determined before application in a clinical setting. To improve the efficacy of cancer treatment, Dr. Joshua D. Schoenfeld and his team of researchers at The University of Iowa recently studied the effects of high levels of ascorbate in patients with glioblastoma (GBM) and non-small-cell lung cancer (NSCLC).

The team exposed NSCLC and GBM cells to high levels of ascorbate and compared the results to normal lung and brain cells after the same exposure. Exposure to approximately 15 picomoles/cell of ascorbate caused NSCLC survival to drop to almost a thousandth of its original population, whereas normal lung cell survival remained at a tenth of its original population. Differences between GBM and normal brain cell survival were much more drastic – exposure to approximately 50 picomoles/cell completely killed the GBM population, while normal brain cell population remained approximately 80% to 90% of its original size. The significant difference between the cancer and normal surviving populations shows ascorbate’s ability to target cancer cells.

Safety of ascorbate treatment combined with chemotherapy in humans was also tested in 11 cancer patients. Each of them received three ascorbate infusions per week for two months and two infusions per week for seven months to reach a plasma concentration of 20 mM. The patient’s average lifespan after diagnosis was 21.5 months, compared to the historical median of 14 months. Although sample size was relatively small, the ascorbate treatment was overall non-detrimental towards patients and actually increased their lifespans.

Despite being in its preliminary stages, ascorbate treatment shows promise in enhancing cancer therapies. Further studies will need to apply this treatment to larger sample sizes to prove its efficacy in humans, but this current study gives support that ascorbate selectively targets and kills cancer cells.

References:

1. J.D. Schoenfeld, et al., O2⋅− and H2O2-mediated disruption of Fe metabolism causes the differential susceptibility of NSCLC and GBM cancer cells to pharmacological ascorbate. Cancer Cell 31, 487-500 (2017). doi: 10.1016/j.ccell.2017.02.018.
2. Image retrieved from: https://www.flickr.com/photos/elwillo/6770150953.