Enhancement of ascorbate cytotoxicity by chelation with ferrous ions through prolonged duration of the action.
Fe(II)-L-ascorbic acid complex (FeAsc) exhibited a greater cytotoxicity [50% inhibitory dose (IC50), 24-32 microM] to human carcinoma A 549 or rat SV40-transformed W3Y cells than ascorbic acid (Asc) (IC50, 460-660 microM); a simple mixture of Fe(II) and Asc, or Fe(II) alone was also less cytotoxic. Malignant cells from a variety of tissues of different species were also susceptible to FeAsc. FeAsc exhibited a longer half-life (66-82 hours) during cell contact than that of Asc (2.5-3.1 hours). Thus chelated Fe(II) but not unbound Fe (II) was responsible for the enhanced cytotoxicity of FeAsc, which was attributed primarily to its prolonged duration of action.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003692:Delayed-Action Preparations; D005296:Ferrous Compounds / Q000627:therapeutic use*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000188:drug therapy; D051381:Rats; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005296:Ferrous Compounds; C051140:iron(II)-ascorbic acid complex; D001205:Ascorbic Acid