Copper, but not iron, enhances apoptosis-inducing activity of antioxidants.

Addition of either CuCl or CuCl2 significantly enhanced sodium ascorbate or sodium 5,6-benzylidene-L-ascorbate (SBA)-induced cytotoxicity and internucleosomal DNA cleavage in human promyelocytic leukemic HL-60 cells. On the other hand, the addition of either FeCl2 or FeCl3 inhibited the cytotoxic activity of ascorbate. These effects were observed even if the cells were exposed for only 20 minutes to metals and ascorbates. Copper also stimulated the gallate or caffeate-induced apoptotic cell death, whereas iron was inhibitory. Both copper and iron enhanced the radical intensity of ascorbates, but slightly reduced the radical intensity of gallate and caffeate, suggesting that radical intensity is not the sole determinant of apoptosis induction. Metals did not significantly change the methionine oxidation stimulated by ascorbate, gallate or caffeate. Methionine oxidation may not be indispensable for antioxidant-induced apoptosis.