Recent studies have revealed the scientific basis for the use of intravenous (i.v.)
vitamin C or
ascorbic acid (ascorbate) in treating
cancers, and raised the possibility of using i.v. ascorbate as a prooxidant anticancer
therapy. Through the production of H2O2, pharmacologic ascorbate can induce some
cancer cell death in vitro and inhibit a number of types of
tumor growth in animal models. However, the mechanism of cell death triggered by ascorbate is not well understood. In this study, we investigated the cytotoxicity of pharmacological concentrations of ascorbate to human
prostate cancer cells and the mechanisms involved. The results showed that ascorbate in the millimolar range induced cytotoxicity in five of the six tested
prostate cancer cell lines. The IC50 values in the sensitive
prostate cancer cells ranged from 1.9 to 3.5 mmol/l, concentrations clinically achievable with i.v. ascorbate use. All tested
androgen-independent cells were sensitive to ascorbate treatment. The ascorbate-insensitive cell line LaPC4 is hormonally dependent. Whereas the reasons for sensitivity/resistance to ascorbate treatment need to be investigated further, cell death in sensitive cells was dependent on H2O2. Ascorbate treatment depleted
ATP and induced autophagy in sensitive
prostate cancer cells, resulting in cell death. Taken together with previous studies, high-dose ascorbate has the potential to be a novel treatment option to
hormone-refractory
prostate cancer.