Although JNK is typically known to activate caspase-3, its inhibition may paradoxically increase caspase-3 levels in particular cancer and neuronal cells under chronic stress conditions by disinhibiting other pro-apoptotic signals such as p38 or intrinsic mitochondrial pathways, triggering the activation of caspase-9 as well as downstream caspase-3 [33]. Here, MAPK8 is linked to cancer.