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.