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Diethyldithiocarbamate Suppresses an NF-κB Dependent Metastatic Pathway in Cholangiocarcinoma Cells

  • Srikoon, Pattaravadee (Division of Hematopoiesis, Center for AIDS Research, Kumamoto University) ;
  • Kariya, Ryusho (Division of Hematopoiesis, Center for AIDS Research, Kumamoto University) ;
  • Kudo, Eriko (Division of Hematopoiesis, Center for AIDS Research, Kumamoto University) ;
  • Goto, Hiroki (Division of Hematopoiesis, Center for AIDS Research, Kumamoto University) ;
  • Vaeteewoottacharn, Kulthida (Division of Hematopoiesis, Center for AIDS Research, Kumamoto University) ;
  • Taura, Manabu (Division of Hematopoiesis, Center for AIDS Research, Kumamoto University) ;
  • Wongkham, Sopit (Department of Biochemistry and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University) ;
  • Okada, Seiji (Division of Hematopoiesis, Center for AIDS Research, Kumamoto University)
  • Published : 2013.07.30

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-${\kappa}B$) has been previously demonstrated in CCA. It is therefore a potential target for CCA treatment. Effects of diethyldithiocarbamate (DDTC) on NF-${\kappa}B$-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 adhesiond. Anti-proliferation, anti-migration and anti-adhesion activities were determined in CCA cell lines, along with p65 protein levels and function. NF-${\kappa}B$ 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-${\kappa}B$ DNA binding, and impaired activity. Moreover, suppression of ICAM-1 expression supported NF-${\kappa}B$-dependent anti-metastatic effects of DDTC. Taken together, DDTC suppression of CCA migration and adhesion through inhibition of NF-${\kappa}B$ signaling pathway is suggested from the current study. This might be a promising treatment choice against CCA metastasis.

Keywords

Diethyldithiocarbamate;cholangiocarcinoma;NF-${\kappa}B$;metastasis;migration;adhesion

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