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

Despite considerable efficacy of arsenic trioxide (As₂O₃) in acute promyelocytic leukemia (APL) treatment, other non-APL leukemias, such as chronic myeloid leukemia (CML), are less sensitive to As₂O₃ treatment. However, the underlying mechanism is not well understood. Here we show that relative As₂O₃-resistant K562 cells have significantly lower ROS levels than As₂O₃-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 As₂O₃. Interestingly, knockdown of peroxiredoxin 1/2/6 did not increase the susceptibility of K562 cells to As₂O₃. On the contrary, knockdown of catalase markedly enhanced As₂O₃-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 As₂O₃ in CML treatment. [ABSTRACT FROM AUTHOR]