we confirmed that snake venom toxin induced generation of ROS, and the antioxidant NAC abolished the upregulation of DR4 and DR5 induced by snake venom toxin, and cell growth inhibitory effect by SVT Cediranib ic50 was also reversed by treatment of NAC. A few studies demonstrated that ROS is also important for your activation of JNK pathway in cancer cell apoptosis. The truth is, ROS dependent activation of JNK is involved in apoptosis, autophage, natural immunity and lifetime restriction. Indeed, the actions of ROS and JNK induced by death receptors seem to be related, both being required participants within the same death inducing pathway triggered by these receptors. It’s been demonstrated that several chemotherapeutic agents including surfactin and celastrol induced apoptosis by induction of ROS through activation of JNK pathway in cancer cells. Thus it’s also possible that improved ROS by snake venom toxin activates JNK pathway which resulted in up-regulation of DR5 and DR4 ultimately causing increase cell death signals. In this study, Neuroblastoma we showed that the JNK is activated by cure of snake venom toxin in both HCT116 and HT29 cell lines. More over, JNK inhibitor SP600125 removed snake venom toxin induced DR4 and DR5 appearance. We also showed that the NAC abolished snake venom toxininduced JNK phosphorylation accompanied with the service of DR4 and DR5. These data claim that activated ROS and consequent activation of JNK might be involved with increased DR4 and DR5 phrase. Similar HSP60 inhibitor to your results, other groups showed that the tocotrienols induced apoptosis of breast cancer cells by upregulation of DR5 by activation of JNK, p38 MAPK and C/EBP homologous protein. Silencing either JNK or p38 MAPK reduced the upsurge in CHOP and DR5 term, and blocked tocotrienols induced apoptosis. It’s been also reported that the LY303511 up-regulated DR4 and DR5 by activation of JNK in neuroblastoma cells, and the induction of DRs were reduced by treatment of JNK and ERK inhibitors. It was also reported the bisindolylmaleimide induced the DR5 by activation of p38 pathways and JNK in astrocytoma cell death. And like our studies, other group suggested that melittin, a bee venom toxin compound increased TRAIL induced apoptosis by activating JNK/p38 path. Transcriptional regulation of DR4 and DR5 is complex, and multiple possible binding websites of various transcription factors, including p53, exist in the upstream region of DR5 and DR4. But, we found that the p53 isn’t induced by snake venom toxin. Thus, the induction of DR5 and DR4 by snake venom toxin occurs independent of p53 in cancer of the colon cells. As an alternative, our data indicate that snake venom toxin induced upregulation of DR4 and DR5 might be influenced by the ROS and JNK pathway. Taken together, our results provide the research that snake venom toxin therapy results in induction of apoptosis of colon cancer cells through ROS and JNK mediated upregulation of DR4 and DR5. These results also show that snake venom toxin may possibly sensitize a cancerous colon cells for the TRAIL induced apoptosis.