Enhancement of antitumor activity of ascorbate against Ehrlich ascites tumor cells by the copper:glycylglycylhistidine complex.
Ascorbate in an aqueous solution is easily oxidized by molecular oxygen in the presence of cupric ion, thus producing reactive oxygen species and exhibiting cytotoxicity. In order to increase the antitumor activity of ascorbate, we used the innocuous form of cupric ion complexed with glycylglycylhistidine, a tripeptide designed to mimic the specific Cu(II) transport site of albumin molecule. Although this square planar copper:glycylglycylhistidine complex did not significantly oxidize ascorbate at pH 7.4, it killed Ehrlich ascites tumor cells in vitro in a high concentration of ascorbate. The injections of large doses of ascorbate together with copper: glycylglycylhistidine prolonged the life span of mice inoculated i.p. with Ehrlich tumor cells. The target specificity against tumor cells was primarily attributable to their high peptide-cleaving activity.
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism / Q000627:therapeutic use*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000627:therapeutic use*; D004357:Drug Synergism; D004578:Electron Spin Resonance Spectroscopy; D007700:Kinetics; D051379:Mice; D009842:Oligopeptides / Q000627:therapeutic use*; D010084:Oxidation-Reduction
D009842:Oligopeptides; C037026:diglycyl-histidine; D003300:Copper; D001205:Ascorbic Acid