Schematic representation of the role of redox homeostasis in Shikonin-treated acute promyelocytic leukemia HL-60 cells. Low doses (<100 ng/mL) of Shikonin exert very mild oxidative stress via unique modulation of the Nrf2/ARE pathway by shifting the cells from proliferation to differentiation. However, higher concentrations of Shikonin result in the predominance of cell death because the oxidative stress is more severe and overcome the antioxidative capacity of Nrf2/ARE pathway, resulting in cell death.