Journal
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
Volume 18, Issue 12, Pages 1779-1791Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1871520618666180604093802
Keywords
Oxidative stress; antioxidant defence system; Nrf2; curcumin; anaerobic metabolism; NF-kappa B; c-Myc; proinflammatory cytokines
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Funding
- Department of Science and Technology, Government of India [-SR/S0/AS-97/2007]
- DST-FIST
- UGC-CAS program
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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-kappa B. 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-kappa B 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-kappa B, expression of COX2, HIF-1 alpha 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-kappa B binding elements of IL-1 alpha, IL-1 beta, TNF-alpha 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-kappa B signaling and expression of proinflammatory cytokines in Dalton's lymphoma ascites cells in vivo.
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