Effect of High-dose Ascorbic Acid on Prostate Cancer Cells and Angiogenesis
Objective: Ascorbic acid (AA), at physiological concentrations, is a well known anti-oxidant but, at higher concentrations, it can be selectively toxic to cancer cells. Controversial data have shown that administration of intravenous high-dose AA can improve therapeutic outcomes in cancer patients. These effects are thought to occur mainly due to direct cytotoxicity mediated by generation of reactive oxygen species. The anti-tumour effects of AA can also be due to inhibition of angiogenesis,
... of angiogenesis, however, this has been poorly studied. This study aimed to investigate the effect of AA on prostate cancer cells and angiogenesis. Materials and Methods: Hormone resistant and naïve human prostate cancer cell lines (PC-3 and LnCaP, respectively) were treated with different concentrations of AA. Cell viability was determined by the resazurin assay. Polymer scaffolds that releases lower (0.01 g/g polymer) and higher (0.1 g/g polymer) concentrations of AA were used to evaluate the effects of AA on angiogenesis. Angiogenesis was investigated by an in vivo chick chorioallantoic membrane assay. Results: AA was toxic to PC-3 and LnCaP prostate cancer cell lines in a dose-dependent manner. Confluent cultures of LnCaP was more sensitive to high-dose AA, while confluent cultures of PC-3 were resistant. There was a biphasic in vivo angiogenic response to AA, that is, while high-dose of AA inhibited angiogenesis, low dose AA stimulated angiogenesis. In addition, a stable form of AA (ascorbate-2 phosphate) was not angiostatic at high concentrations, suggesting that angiostatic actions of high-dose AA may be due to its direct toxicity on endothelial cells. Conclusion: We demonstrated that AA was toxic to prostate cancer cell lines, and inhibits angiogenesis at high doses. Further in vivo studies are required to validate these finding before any clinical inference can be made.