title: Diethyldithiocarbamate suppresses an NF-kappaB dependent metastatic pathway in cholangiocarcinoma cells.
abstract: Cholangiocarcinoma (CCA) is a tumor of biliary ducts, which has a high mortality rate and dismal prognosis. Constitutively activation of the transcription factor nuclear factor kappa-B (NF-κB) has been previously demonstrated in CCA. It is therefore a potential target for CCA treatment. Effects of diethyldithiocarbamate (DDTC) on NF-κB-dependent apoptosis induction in cancer have been reported; however, anti-metastasis has never been addressed. Therefore, here the focus was on DDTC effects on CCA migration and adhesion. Anti-proliferation, anti-migration and anti-adhesion activities were determined in CCA cell lines, along with p65 protein levels and function. NF-κB target gene expression was determined by quantitative RT-PCR. DDTC inhibited CCA cell proliferation. Suppression of migration and adhesion were observed prior to anti-CCA proliferation. These effects were related to decreased p65, reduction in NF-κB DNA binding, and impaired activity. Moreover, suppression of ICAM-1 expression supported NF-kB-dependent anti-metastatic effects of DDTC. Taken together, DDTC suppression of CCA migration and adhesion through inhibition of NF-κB signaling pathway is suggested from the current study. This might be a promising treatment choice against CCA metastasis.
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Pattaravadee
authors.initials: P
authors.lastname: Srikoon
authors.forename: Ryusho
authors.initials: R
authors.lastname: Kariya
authors.forename: Eriko
authors.initials: E
authors.lastname: Kudo
authors.forename: Hiroki
authors.initials: H
authors.lastname: Goto
authors.forename: Kulthida
authors.initials: K
authors.lastname: Vaeteewoottacharn
authors.forename: Manabu
authors.initials: M
authors.lastname: Taura
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004050:Ditiocarb / Q000494:pharmacology*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014945:Wound Healing
chemical_list: D002614:Chelating Agents; D016328:NF-kappa B; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D004050:Ditiocarb