GROWTH-CONTROL OF HUMAN COLON-TUMOR XENOGRAFTS BY ASCORBIC-ACID, COPPER, AND IRON

We have previously reported that ascorbic acid or a combination of ascorbic acid and cupric sulfate was able to inhibit the growth of human mammary and lung tumor xenografts in mice. In the present study, the 6-day subrenal capsule assay method was used to investigate the effect of ascorbic acid, cupric sulfate and ferric chloride on the growth of a human colon tumor in mice, The method permits the observation of changes in the size of tumor fragments implanted beneath the renal capsule of mice, without the effective intervention of the immune system. Results of dose-response experiments indicate that tumor growth was inhibited when mice were fed a diet containing ascorbic acid (4 to 10 g/kg body weight/day) in combination with cupric sulfate (2 to 4 mg/kg body weight/day) or ferric chloride (2 to 8 mg/kg body weight/day), Ascorbic acid alone was much less effective, Copper and iron alone enhanced tumor growth. Since cupric or ferric ion is a catalyst for the oxidation of ascorbic acid, the results support the suggestion that the antitumor mechanism involved a pro-oxidative effect of ascorbic acid on the tumor. The observed antitumor activity is not due to the metabolism of ascorbic acid as a vitamin, but due to its chemical properties. The tumor-inhibiting effect seems to be a direct growth suppressive action of ascorbic acid oxidation and certain degradation products of ascorbic acid, which are formed in vitro and are not formed by the metabolism of ascorbic acid.