Curcumin inhibits superoxide dismutase-induced epithelial-to-mesenchymal transition via the PI3K/Akt/NF-κB pathway in pancreatic cancer cells

Li,Wei; Jiang,Zhengdong; Xiao,Xue; Wang,Zheng; Wu,Zheng; Ma,Qingyong; Cao,Lei

doi:10.3892/ijo.2018.4295

Curcumin inhibits superoxide dismutase-induced epithelial-to-mesenchymal transition via the PI3K/Akt/NF-κB pathway in pancreatic cancer cells

Authors:
- Wei Li
- Zhengdong Jiang
- Xue Xiao
- Zheng Wang
- Zheng Wu
- Qingyong Ma
- Lei Cao
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Affiliations: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China
Published online on: March 1, 2018 https://doi.org/10.3892/ijo.2018.4295
Pages: 1593-1602

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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.

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