Given by injection, it could potentially be a safe, effective and low-cost treatment for ovarian and other cancers, scientists at the University of Kansas say.
Reporting in Science Translational Medicine, they call for large-scale government clinical trials.
Pharmaceutical companies are unlikely to run trials, as vitamins cannot be patented.
Vitamin C has long been used as an alternative therapy for cancer.
In the 1970s, chemist Linus Pauling reported that vitamin C given intravenously was effective in treating cancer.
However, clinical trials of vitamin C given by mouth failed to replicate the effect, and research was abandoned.
It is now known that the human body quickly excretes vitamin C when it is taken by mouth.
However, scientists say that when given by injection vitamin C is absorbed into the body, and can kill cancer cells without harming normal ones.
The researchers injected vitamin C into human ovarian cancer cells in the lab, into mice, and into patients with advanced ovarian cancer.
They found ovarian cancer cells were sensitive to vitamin C treatment, but normal cells were unharmed.
The treatment worked in tandem with standard chemotherapy drugs to slow tumor growth in mouse studies. Meanwhile, a small group of patients reported fewer side-effects when given vitamin C alongside chemotherapy.
Co-researcher Dr. Jeanne Drisko said there was growing interest in the use of vitamin C by oncologists.
One potential hurdle is that pharmaceutical companies are unlikely to fund trials of intravenous vitamin C because there is no ability to patent natural products.
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