Curcumin Modulates Glycolytic Metabolism and Inflammatory Cytokines via Nrf 2 in Dalton's Lymphoma Ascites Cells In Vivo.

Abstract

Warburg effect is characterized by the upregulation of HIF-1 and c-Myc regulated LDH-A, even aerobically owing to hypoxic environment and alterations in oncogenes or tumor suppressor genes in cancer. Reduced antioxidant defence system in transformed cells favors higher ROS production, which plays a significant role in carcinogenesis and acts as an important regulator of NF-κB. In addition, various proinflammatory cytokines play active roles in maintenance and progression of cancer. In continuation with our previous studies illustrating the long-term effect of curcumin using a liver tissue, present study was aimed to elucidate the anti-cancer effect of curcumin due to its long-term effect in the regulation of glycolytic metabolism, NF-κB activation, expression of proinflammatory cytokines in Dalton's lymphoma ascites cells in vivo. Spectrophotometric assays, RT-PCR and EMSA were performed to address the problems. Results revealed that curcumin-induced activation of antioxidant enzymes, Nrf2 and downstream signaling gene NQO1. Reduction of oxidative stress, down-regulation of NADPH: Oxidase, decline in ROS and H2O2 levels were also observed. Activation of NF-κB, expression of COX2, HIF-1α and cMyc, as well as expression and activity of LDH-A were significantly reduced by curcumin. Besides, expression of proinflammatory cytokines was significantly down-regulated via reducing binding of nuclear protein with AP-1, NF-IL6, ETS and NF-κB binding elements of IL-1α, IL-1β, TNF-α and IL-6 promoters, respectively. Curcumin downregulates glycolytic metabolism via modulation of stress-activated genes and reduces oxidative stress by enhancing antioxidant defence system, which inhibits activation of NF-κB signaling and expression of proinflammatory cytokines in Dalton's lymphoma ascites cells in vivo.