Effect of copper and iron ions on cytotoxicity induced by ascorbate, gallate and caffeate.

Four antioxidants, sodium ascorbate, gallic acid, n-propyl gallate and caffeic acid, induced apoptotic cell death in human promyelocytic leukemic HL-60 cells. The effects of all these compounds were enhanced by CuCl2 or deferoxamine mesylate, an iron chelator, but were reduced by FeCl3. ESR spectroscopy showed that both CuCl2 and FeCl3 enhanced the ascorbyl radical intensity, but reduced the gallate and caffeate radical intensity. The present data demonstrate that copper and iron ions modify the cytotoxic activity of these antioxidants differently and their radical intensity is not the sole determinant of cytotoxic activity.