Curiously, knock-down of DR4 more dramatically changed the growth inhibitory influence of snake venom toxin in HCT116 and HT 29 cells. We also showed that the caspase 3 activation was inhibited by cure of DR4 or DR5 siRNA followed with downregulation of DR4 or DR5 proteins. These results indicate that DR4 and DR5 play a major role in apoptotic colon cancer cell death by snake E3 ubiquitin ligase inhibitor venom toxin. We discovered that the JNK was activated by cure of snake venom toxin, although not ERK and p38 in HT and HCT116 29 cancer of the colon cells. To further examine whether JNK plays a crucial role in snake venom toxin induced up regulation of DR4 and DR5, we pretreated the cancer of the colon cells with SP600125, a JNK inhibitor for 1 h, and then these cells treated with snake venom toxin for 24 h to assess cell viability and DR4 and DR5 expression. As a result, JNK inhibitor abolished snake venom toxin induced inhibition of cell viability and suppressed the snake RNAP venom toxin induced up regulation of DR4 and DR5, suggesting that JNK path could be involved in snake venom toxin induced apoptosis and up-regulation of DRs. Since we already showed that snake venom toxin induced ROS in a dose dependent fashion in HCT116 and HT 29 cells in Figure 2A, we further examined whether ROS plays a part in snake venom toxin induced up-regulation of DR4 and DR5. We pre-treated with NAC, an antioxidant for 1 h in HT and HCT116 29 cells, and then treated with snake venom toxin for 30 min to evaluate DR5 appearance and cell viability and DR4. It was discovered that NAC abolished snake venom toxin Enzalutamide distributor induced inhibition of cell viability and suppressed the snake venom toxin induced up-regulation of DR4 and DR5, and JNK phosphorylation, indicating that ROS can be involved with snake venom toxininduced apoptosis and upregulation of DRs, and activation of JNK. Taken together, these results indicated that the JNK and ROS route are essential in induction of DR5 and DR4 expression, and DR4 and DR5 mediated apoptosis by snake venom toxin in cancer of the colon cells. We confirmed that snake venom toxin inhibited HCT116 and HT 29 a cancerous colon cell growth through apoptosis. Our study also showed that this effect was linked to the JNK and ROS mediated enhanced expression of the DR5 and DR4. The TRAIL receptors, DR4 and DR5 are also expressed in colon carcinomas and their expressions are improved as tumor cells acquire malignant potential. Tumor and colon cancer cells are relatively sensitive and painful to TRAIL mediated apoptosis, but typical colonic epithelium are immune to TRAILmediated apoptosis. Because of its particular ability for killing of tumefaction cells with small negative effects on normal cells, the activators of TRAIL pathway have emerged as attractive candidates for cancer therapy. It’s been shown that TRAIL induced apoptosis might be enhanced by chemotherapy in several in vitro and xenograft models of cancer, an effect noted to be mediated through enhanced DR4 and DR5 phrase.