Superoxide dismutase is an enzyme responsible for dismutating superoxide radicals, which are generated in the mitochondria by ETC complex I and complex III. Over-expression of SOD has been shown in lung tumors as compared to normal tissues suggesting its role in lung carcinogenesis. Moreover, SOD was recently identified as a target for the selective killing of cancer cells. Our results clearly show that capsaicin treatment significantly decreased SOD activity in BxPC-3 cells and AsPC-1 tumor xenografts. Glutathione peroxidase is an important enzyme that utilizes GSH as a substrate to detoxify intracellular 4-(Benzyloxy)phenol peroxides Atropine sulfate including hydrogen peroxide. Capsaicin treatment resulted in the significant inhibition of GPx activity and expression in BxPC-3 cells. These results indicate that capsaicin deplete GSH level and inhibit GSH dependent anti-oxidant enzymes resulting in the accumulation of ROS in pancreatic cancer cells leading to mitochondrial damage. In addition catalase is another important enzyme which is responsible for detoxifying hydrogen peroxide to water. Consistently, we observed that PEG-SOD, PEG-catalase, catalase or EUK-134 prevented capsaicin mediated ROS generation by complex-I and complex-III, ATP depletion, mitochondrial damage and apoptosis, indicating the involvement of catalase. As a proof-of-concept, over-expression of catalase by transient transfection completely blocked capsaicin mediated ROS generation and apoptosis in BxPC-3 cells demonstrating its critical role in the survival of pancreatic cancer cells. Most of the cancer cells have higher levels of ROS that 
helps in proliferation and cell growth. Due to elevated ROS, cancer cells are highly dependent on their antioxidant system to maintain redox balance and hence are more susceptible to further oxidative stress. In contrast, normal cells are more resistant to oxidative stress due to the fact that these cells have lower levels of ROS and increased levels of antioxidants. Hence any agent that increases intracellular ROS in cancer cells may increase ROS to a toxic level resulting in mitochondrial damage and cell death as shown in our model. It is noteworthy that several agents such as Elesclomol or Trisenx are currently being used for the treatment of metastatic melanoma and acute promyelocytic leukemia respectively. Both of these agents selectively kill cancer cells by increasing ROS generation. We and others have shown previously that administration of 2.5 or 5 mg/kg capsaicin orally or subcutaneously suppress pancreatic and prostate tumor xenografts in vivo respectively. In the present study, 2.5 mg/kg capsaicin was given to mice by oral gavage, which is 0.202 mg/kg when converted to human equivalent dose and equates to 13.2 mg dose of capsaicin for a 60 kg person. However, further pharmacokinetic, bioavailability and clinical studies are needed to validate these correlations. Taken together our studies provide detailed mechanism how capsaicin treatment causes ROS generation through mitochondria and depleted intracellular antioxidants resulting in mitochondrial damage and apoptosis in pancreatic cancer cells. On the other hand, normal pancreatic epithelial cells were resistant to the effects of capsaicin. CNTF promotes the survival of a variety of neurons and oligodendrocytes, and induces neurite outgrowth and axon regeneration in both developing and mature nervous system. In addition, it appears to be an effective neuroprotective agent in animal models of CNS neurodegenerative diseases. CNTF has also been reported to activate leptin-like pathways in the brain and reduce body fat and stress in a leptin-independent manner. In the vertebrate retina, CNTF exhibits numerous effects on the development, differentiation and survival of retinal neurons. CNTF appears to play a critical role in progenitor commitment to the rod photoreceptor cell fate and in photoreceptor differentiation. It is reported to increase the long-term survival of retinal ganglion cells after axotomy. Furthermore, CNTF is capable of retarding retinal degeneration in several animal models of retinitis pigmentosa.