“…Apoptosis induction under all conditions was blocked by the NADPH oxidase (NOX) inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF) and the hydroxyl radical scavenger mannitol, in line with the established central role of superoxide anions and hydroxyl radicals in both signaling pathways (Heinzelmann and Bauer, 2010;Bauer, 2012). Extracellular catalase activity with modulatory potential, at a concentration that was too low for complete protection against intercellular apoptosis-inducing ROS signaling, was further confirmed for 208Fsrc3 using additional approaches, such as inactivation of catalase by extracellular singlet oxygen (Escobar et al, 1996) generated by the photosensitizer photofrin (data not shown) or by the reactive aldehyde 4-hydroxynonenal (D'Souza et al, 2008;Bauer and Zarkovic, 2015). Extracellular catalase was demonstrated after induction of RAS expression in IR-1 cells (208F rat fibroblasts with an inducible RAS oncogene) (Schwieger et al, 2001), accompanied by NOX1 activation and transformation and in spontaneously transformed hamster embryonal (STHE) fibroblasts (Deichman et al, 1989) (data not shown).…”