title: Curcumin inhibits H2O2-induced invasion and migration of human pancreatic cancer via suppression of the ERK/NF-κB pathway.
abstract: 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-κB (NF-κB) 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-κB 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-κB signaling pathway. This study suggests that curcumin may be a potential anticancer agent for pancreatic cancer.
authors: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors: Lei
authors: L
authors: Cao
authors: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Jiangbo
authors: J
authors: Liu
authors: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Lun
authors: L
authors: Zhang
authors: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China.
authors: Xue
authors: X
authors: Xiao
authors: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Wei
authors: W
authors: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D006861:Hydrogen Peroxide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D003474:Curcumin