FIGURE 8.

Differences between TRAIL- and AD5-10-induced signaling pathways. In the initiation stage of the caspase cascade, FADD and caspase-8 are recruited to DR5 (and possibly DR4) DISC. c-FLIP is involved in DISC formation in non-small cell lung cancer. Moreover, unlike TRAIL and other reported agonistic antibodies for DR5, AD5-10 particularly induces ROS accumulation and time-dependent reduction of GSH and GSSG content in the intrinsic mitochondrial pathway of Jurkat leukemia cells. ROS scavengers, antioxidant (N-acetyl-l-cysteine (NAC)) and GSH, suppress AD5-10-triggered cell death by inhibiting the release of apoptosis-inducing factor (AIF) and endonuclease G (EndoG), which contribute to the fragmentation of the nuclear DNA. Under ROS stress, JNK was triggered simultaneously and a subsequent secondary activation of JNK was observed; NF-κB was also activated during this time course.