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

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.

Curcumin attenuates lncRNA H19‑induced epithelial‑mesenchymal transition in tamoxifen‑resistant breast cancer cells

“…In hepatoma cells, curcumin inhibits TGF-β1-induced EMT by suppressing Smad2 signaling pathway activation (31). A recent study also indicated that curcumin inhibits superoxide dismutase-induced migration, invasion and EMT-related gene expression in pancreatic cancer (32). In the present study, curcumin exerted an inhibitory effect on viability and EMT in MCF-7/TAMR cells and significantly attenuated H19-induced migration, invasion and EMT.…”

Curcumin attenuates hyperglycemia-driven EGF-induced invasive and migratory abilities of pancreatic cancer via suppression of the ERK and AKT pathways

“…For instance, curcumin sensitized gemcitabineresistant cancer cells by inhibiting the expression of the PRC2 subunit EZH2 and its related lncRNA PVT1 (35).We demonstrated that curcumin suppressed hydrogen peroxideinducedcell migration and invasion through the inhibition of the ROS/ERK/NF-κB signaling pathway (17). Curcumin was also found to inhibit superoxide dismutase-induced cancer EMT via the suppression of the PI3K/Akt/NF-κB signaling pathway in pancreatic cancer cells (14). In the present study, our data showed that curcumin inhibited the invasive and migratory abilities of pancreatic cancer cells under high glucose conditions, which maybe attributed to the EGF/ERK and EGF/Akt signaling pathways.…”

“…Curcumin exhibits its antitumor effects via targeting multiple signaling pathways, including mitogen-activated protein kinase (MAPK), protein kinase B (Akt) and others (13). In a recent study, it was indicated that curcumin plays an important role in suppressing superoxide dismutase-induced EMT of pancreatic cancer by inhibiting the PI-3K/Akt/NF-κB signaling pathway (14). It was also confirmed that curcumin could restrain hypoxiainduced EMT via suppression of the hedgehog signaling pathway in pancreatic cancer cells (15).…”

Ferritinophagic Flux Activation in CT26 Cells Contributed to EMT Inhibition Induced by a Novel Iron Chelator, DpdtpA

“…Fe(II) either in lysosome or in labile iron pool (LIP) is known to catalyze Fenton reaction, yielding extremely reactive hydroxyl radicals [12]. As mentioned above, accumulating evidence shows that ROS are involved in EMT transition [13–17]; however, the functions of ROS in the processes of EMT remain unclear.…”