Targeting Catalase but Not Peroxiredoxins Enhances Arsenic Trioxide-Induced Apoptosis in K562 Cells

Despite considerable efficacy of arsenic trioxide (As(2)O(3)) in acute promyelocytic leukemia (APL) treatment, other non-APL leukemias, such as chronic myeloid leukemia (CML), are less sensitive to As(2)O(3) treatment. However, the underlying mechanism is not well understood. Here we show that relative As(2)O(3)-resistant K562 cells have significantly lower ROS levels than As(2)O(3)-sensitive NB4 cells. We compared the expression of several antioxidant enzymes in these two cell lines and found that peroxiredoxin 1/2/6 and catalase are expressed at high levels in K562 cells. We further investigated the possible role of peroxirdoxin 1/2/6 and catalase in determining the cellular sensitivity to As(2)O(3). Interestingly, knockdown of peroxiredoxin 1/2/6 did not increase the susceptibility of K562 cells to As(2)O(3). On the contrary, knockdown of catalase markedly enhanced As(2)O(3)-induced apoptosis. In addition, we provide evidence that overexpression of BCR/ABL cannot increase the expression of PRDX 1/2/6 and catalase. The current study reveals that the functional role of antioxidant enzymes is cellular context and treatment agents dependent; targeting catalase may represent a novel strategy to improve the efficacy of As(2)O(3) in CML treatment.