Cytotoxic effect of ascorbate and its derivatives on cultured malignant and nonmalignant cell lines

The effect of L-ascorbate and its derivatives on the growth of malignant and nonmalignant cell lines has been examined. L-Ascorbate and its oxidative product dehydroascorbate were cytotoxic or lethal to the fast-growing malignant cells, but they were less toxic to nonmalignant cells. Two isomers of ascorbate, D-ascorbate and D-isoascorbate, both with 5% of the antiscorbutic potency and very high turnover rate, had similar activities. The cytotoxic effect of ascorbate was apparently not related to the metabolic or vitamin activities of ascorbate at the cellular level. Furthermore, studies on the viability of treated cells indicated that the observed effect on cell growth was not cytostatic in nature but was the result of a direct cell-killing action of ascorbate. Several groups of ascorbate derivatives were also tested; many of them were toxic to these cells. The results support the hypothesis that the cytotoxic activity of ascorbate was due to its chemical properties and that certain oxidation and degradation products of ascorbate were cytotoxic agents.