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.