Curcumin Modulates Glycolytic Metabolism and Inflammatory Cytokines via Nrf 2 in Dalton's Lymphoma Ascites Cells In Vivo
Background: 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.
Objective: 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.
Method: Spectrophotometric assays, RT-PCR and EMSA were performed to address the problems.
Results: 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.
Conclusion: 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.
Objective: 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.
Method: Spectrophotometric assays, RT-PCR and EMSA were performed to address the problems.
Results: 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.
Conclusion: 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.
Keywords: NF-ΚB; Nrf2; Oxidative stress; anaerobic metabolism; antioxidant defence system; c-Myc; curcumin; proinflammatory cytokines
Document Type: Research Article
Publication date: 01 September 2018
- Editorial Board
- Information for Authors
- Subscribe to this Title
- Ingenta Connect is not responsible for the content or availability of external websites
- Access Key
- Free content
- Partial Free content
- New content
- Open access content
- Partial Open access content
- Subscribed content
- Partial Subscribed content
- Free trial content