EFFECT OF ASCORBIC-ACID AND ITS DERIVATIVES ON THE GROWTH OF HUMAN MAMMARY-TUMOR XENOGRAFTS IN MICE

Experiments with human or laboratory animals indicated that ascorbic acid had antitumor activities. The antitumor activity of ascorbic acid in animals or in cultured cells was increased in the presence of cupric ion, a catalyst for the oxidation of ascorbic acid. The effect of ascorbic acid and its derivatives on the growth of a human mammary tumor in mice was investigated using the 6-day subrenal capsule assay method. The results indicated that intraperitoneal injection of a mixture of ascorbate (150 mg/kg body weight/day) and cupric sulfate (3 mg/kg body weight/day) significantly inhibited tumor growth in immunocompetent mice, whereas neither alone was effective. The antitumor activity of D-isoascorbic acid, an isomer of ascorbic acid, with 5% of the antiscorbutic potency and very high turnover rate, is similar to that of ascorbate. This suggests that the anticancer activity of ascorbic acid was not due to the metabolism of ascorbic acid as a vitamin, but due to its chemical properties. Dehydroascorbic acid, the oxidation product of ascorbic acid, had antitumor activity. Among the twelve other ascorbic acid derivatives tested, six of them had antitumor activities. The results support the hypothesis that certain oxidation or degradation products of ascorbic acid were active antineoplastic agents. The tumor-inhibiting effect seems to be a direct growth depression action of certain degradation products of ascorbic acid, which are formed in vitro and are not formed by the metabolism of ascorbic acid.