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.
Long-term Effect of Silver Powder in vivo