Abstract
Curcumin is a natural polyphenol compound derived from turmeric. It possesses multiple pharmacological properties, including antioxidant, anti-inflammatory and anti-tumor progression properties. Our recent study demonstrated that superoxide dismutase (SOD)-dependent production of hydrogen peroxide (H2O2) promoted the invasive and migratory activity of pancreatic cancer cells. However, whether curcumin suppresses SOD-induced cancer progression and the related mechanisms remains unclear. Since epithelial‑to-mesenchymal transition (EMT) plays a key role in tumor metastasis, the aim of the present study was to examine whether curcumin intervenes with SOD-induced EMT in pancreatic cancer and the underlying mechanism. The human pancreatic cancer cells BxPC-3 and Panc-1 were exposed to SOD in the presence or absence of curcumin, catalase (CAT, a scavenger of H2O2), or LY 294002 [a phosphoinositide-3 kinase (PI3K) inhibitor]. Intracellular reactive oxygen species (ROS) and H2O2 were evaluated by 2,7-dichlorodihydrofluorecein diacetate and H2O2 assay, respectively. The activation of p-Akt and p-nuclear factor (NF)-κB were examined by western blotting. The migratory and invasive abilities of pancreatic cancer cells were tested by the wound healing and Transwell invasion assays. The expression of E-cadherin, N-cadherin and vimentin (EMT-related genes) were measured by reverse transcription-quantitative polymerase chain reaction and western blotting at the mRNA and protein levels, respectively. The findings of the present study demonstrated that curcumin decreased SOD-induced production of ROS and H2O2 in BxPC-3 and Panc-1 cells. Curcumin was able to suppress SOD-induced invasion and migration, and it also regulated the expression of the above‑mentioned EMT-related genes and cell morphology. SOD-induced cell invasion was also inhibited by catalase and LY 294002. Furthermore, the levels of p-Akt and p-NF-κB caused by SOD could be offset by treatment with curcumin and LY 294002. To summarize, these results demonstrated that curcumin was able to prevent SOD-driven H2O2-induced pancreatic cancer metastasis by blocking the PI3K/Akt/NF-κB signaling pathway. The use of curcumin to inhibit the H2O2/Akt/NF-κB axis may be a promising therapeutic approach to the treatment of patients with pancreatic cancer.