Antiproliferative and DNA-scission activities of L-ascorbic acid in the presence of copper chelates.
L-Ascorbic acid inhibits the growth of mouse neuroblastoma and human endometrial carcinoma cells at concentrations greater than 100 microM. Under the same concentrations used in cell culture study, normal human lung fibroblasts show less sensitivity to the antiproliferative effect of ascorbate than tumor cell lines. The antitumor activity of ascorbate can be greatly potentiated by the combination with copper ions or copper chelates. The exposure of normal and tumor cells to the mixtures of ascorbate and copper chelates, especially Cu2+-o-phenanthroline and Cu2+-2,9-dimethyl-o-phenanthroline complexes, resulted in the killing of a large proportion of cell populations whereas the organic ligand portion of metal complexes was much less toxic. These copper chelates in combination with ascorbate showed different degrees of DNA-scission activities which could not be correlated with their cytotoxicities in the cell culture study. It is suggested that the primary targets of these antiproliferative agents may be on the biological sites such as cell membrane other than DNA in the nucleus which has been commonly assumed as the critical target for most free radical-generating antitumor drugs.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D010582:Bacteriophage lambda; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D004279:DNA, Viral / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008168:Lung; D051379:Mice; D009447:Neuroblastoma; D014594:Uterine Neoplasms
D002614:Chelating Agents; D004279:DNA, Viral; D003300:Copper; D001205:Ascorbic Acid