Transformed cell-derived reactive oxygen species support and inhibit nitric oxide-mediated apoptosis induction.

Nitric oxide has been recently shown to require interaction with extracellular superoxide anions and subsequent peroxynitrite formation for selective apoptosis induction in transformed fibroblasts. In addition to foster NO-mediated apoptosis, transformed target cell-derived reactive oxygen species (ROS) also exhibit a marked inhibitory effect directed against NO-mediated apoptosis. This inhibition can be abrogated by catalase and can be augmented by hydrogen peroxide generation through glucose oxidase. Therefore, transformed fibroblasts at high density seem to inhibit NO-mediated apoptosis through hydrogen peroxide formation. Inhibition of NO-mediated apoptosis can be explained by the interaction of hydrogen peroxide with NO, resulting in the generation of hydroxyl radicals. As hydrogen peroxide as well as NO represent far ranging species, hydroxyl radical generation occurs more likely distant from the cell membrane and therefore does not have an apoptosis-inducing effect on the cells. In total, this reaction is rather blunting apoptosis induction mediated by NO. The interaction of hydrogen peroxide with NO may have consequences for the control of transformed cells by NO-utilizing natural antitumor systems.