Diethyldithiocarbamate Suppresses an NF-κB 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 previouslydemonstrated 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 hasnever been addressed. Therefore, here the focus was on DDTC effects on CCA migration and adhesiond. Antiproliferation,anti-migration and anti-adhesion activities were determined in CCA cell lines, along with p65 proteinlevels and function. NF-κB target gene expression was determined by quantitative RT-PCR. DDTC inhibitedCCA 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-κB-dependent anti-metastatic effects of DDTC. Taken together,DDTC suppression of CCA migration and adhesion through inhibition of NF-κB signaling pathway is suggestedfrom the current study. This might be a promising treatment choice against CCA metastasis.