The canonical NF-κB pathway differentially protects normal and human tumor cells from ROS-induced DNA damage

► H2O2 driven ROS activates NF-κB and arrests normal HDF and A549 tumor cell cycling. ► HDFs prematurely senesce while A549 cells become apoptotic in response to ROS. ► Suppressing NF-κB activation exacerbates the ROS-mediated HDF senescence response. ► Inhibiting canonical NF-κB enhances ROS-induced A549 tumor cell apoptosis. ► The p53-p21Cip1/Waf1 axis drives the ROS-mediated senescence response of HDFs.