Anti-Cancer Activity of Piperine Against Colon Carcinogenesis Via Modulation of NF-κB/Nrf-2/Keap1/HO-1 Signalling Pathways

Abstract Background: Colon cancer is the most common cancer in men and women globally, killing millions of people annually. Though widespread development has been made in the management of colorectal cancer, still there is an urgency to find novel targets for effective treatment of these patients. Piperine is an alkaloid found in black pepper having anticancer, anti-oxidant and anti-inflammatory activities. Nuclear factor-erythroid 2–kelch-like ECH-associated protein 1(Nrf-2/Keap1)/ Heme-oxygenase1 (HO-1) signaling pathway plays a vital part in shielding cells from the injury of intracellular oxidative stress and inflammation. A potential cross-talk between Nrf-2 and NF-κB pathways is recognized during cancerous growth and expansion. We studied this pathway extensively in the present study to discover novel targets in prevention of chemically induced colon cancer with piperine.Results: We found that NF-κB inhibition occurs by the activation of Nrf-2 blocks downstream inflammatory mediators/cytokines (TNF-α, IL-6, IL-1β, Cox-2, PGE2, iNOS, NO, MPO) and triggers antioxidant response machinery (HO-1, NQO-1 GSH, GR, GPx, CAT, SOD), scavenges ROS, decreases lipid peroxidation. Histological findings further validated our defensive effects of piperine on colon carcinogenesis. Piperine down-regulates CEA, MDF and ACF, markers of precancerous lesions in colon.Conclusion: Our results indicate that piperine may be an effective molecule for the prophylactic treatment of colon carcinogenesis by targeting NF-κB/Nrf-2/Keap1/HO-1 pathway as a progressive strategy in preclusion and effective treatment of colorectal cancer.