FIG. 5.

The prosurvival response of normal HSCs to mild pro-oxidants has led to the concept of differential response to redox cycling compounds between normal and malignant HSCs. Redox-active compounds will use the normal levels of ROS produced by healthy HSCs to activate an antioxidant response leading to increased proliferation and HSC function. Conversely, LSCs perpetually produce elevated levels of superoxide via aberrant constitutive enzyme activity that can be used by redox-active compounds to produce second messenger ROS such as hydrogen peroxide. This may lead to LSC senescence and death. The theoretical result is the protection of normal HSC function with simultaneous cytotoxic, anticancer affects in the LSC population. AP-1, activating protein-1. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars