Curcumin inhibits H2O2-induced invasion and migration of human pancreatic cancer via suppression of the ERK/NF-κB pathway

Curcumin (diferuloylmethane), a natural polyphenol present in turmeric, possesses a wide spectrum of pharmacological properties, including antioxidant and antitumor metastatic activities. However, the underlying mechanisms by which curcumin suppresses the metastasis of pancreatic cancer are still not fully elucidated. Our previous study demonstrated that a moderate amount of hydrogen peroxide (H2O2) is able to promote pancreatic cancer invasion. The aim of this study was to determine whether curcumin can suppress H2O2-induced tumor invasive and migratory abilities. Human pancreatic cancer BxPC-3 and Panc-1 cells were exposed to H2O2 with or without curcumin or N-acetylcysteine (NAC; a scavenger of free radicals). The effects of curcumin on pancreatic cancer cell proliferation was analyzed using MTT assay. The intracellular reactive oxygen species (ROS) was determined using 2,7-dichlorodihydrofluorecein diacetate. The cellular invasive and migratory abilities were analyzed using Transwell Matrigel invasion assay and wound healing assay, respectively. The expressions of matrix metalloproteinase (MMP)-2 and MMP-9 were determined using qT-PCR and western blotting at mRNA and protein level. The activation of p-extracellular signal-regulated kinase (ERK) and p-nuclear factor-kappa B (NF-kappa B)were measured by western blotting. Our data showed that curcumin inhibited cancer cell proliferation in a dose-dependent manner. Curcumin and NAC were able to inhibit H2O2-induced ROS production, reduce the migration and invasion, and decrease the expression of MMP-2 and MMP-9 in pancreatic cancer cells. In addition, the H2O2-induced elevation of p-ERK and p-NF-kappa B in BxPC-3 and Panc-1 cells were reduced by curcumin, NAC and PD 98059 (an ERK inhibitor). These data indicate that curcumin suppresses pancreatic cancer migration and invasion through the inhibition of the ROS/ERK/NF-kappa B signaling pathway. This study suggests that curcumin may be a potential anticancer agent for pancreatic cancer.