title: Anticancer effect of arsenite on cell migration, cell cycle and apoptosis in human pancreatic cancer cells.
abstract: The standard treatment for advanced pancreatic cancer is chemotherapy, but its clinical outcome remains unsatisfactory. Therefore, the development of novel treatments for this malignancy is urgently required. In the present study, the anticancer effect of arsenite on platelet-derived growth factor (PDGF)-BB-induced migration, cell cycle and apoptosis was investigated in pancreatic cancer cells (AsPC-1 and BxPC-3), and compared with the effect on normal pancreatic epithelial (PE) cells. In the cell migration assay, arsenite clearly inhibited PDGF-BB-induced cell migration in AsPC-1 cells, but not in BxPC-3 or PE cells. Arsenite also caused cell apoptosis in AsPC-1 cells, but not in BxPC-3 or PE cells. In AsPC-1 cells, the levels of cyclin D1 and phosphorylated retinoblastoma protein decreased following treatment with arsenite, but this was not observed in BxPC-3 cells. To further examine the differences between these two cell lines, the effect of arsenite on upstream p44/p42 mitogen-activated protein kinase (MAPK) and Akt was investigated. PDGF-BB caused phosphorylation of p44/p42 MAPK and Akt in both cell lines. Pretreatment with arsenite significantly suppressed PDGF-BB-induced phosphorylation of Akt, but not of p44/p42 MAPK in AsPC-1 cells. By contrast, arsenite did not affect these molecules in BxPC-3 cells. Since the inhibition of the Akt signaling pathway markedly reduced PDGF-BB-induced migration in AsPC-1 cells, the present results strongly suggest that arsenite inhibits PDGF-BB-induced migration by suppressing the Akt signaling pathway in AsPC-1 cells. Therefore, arsenite may be a useful tool for the treatment of patients with certain types of pancreatic cancer, without causing adverse effects on normal pancreatic cells.
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Horibe
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Adachi
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yasuda
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamauchi
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kawaguchi
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Department of Gastroenterology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
keywords: Akt; apoptosis; arsenite; cell migration; pancreatic cancer