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http://dx.doi.org/10.7314/APJCP.2013.14.7.4441

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)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.7, 2013 , pp. 4441-4446 More about this Journal
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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