title: Effects of 5-Aza-2'-Deoxycytidine, Bromodeoxyuridine, Interferons and Hydrogen Peroxide on Cellular Senescence in Cholangiocarcinoma Cells.
abstract: Cellular senescence, a barrier to tumorigenesis, controls aberrant proliferation of cells. We here aimed to investigate cellular senescence in immortalized cholangiocyte and cholangiocarcinoma cell lines using five different inducing agents: 5-aza-2'deoxycytidine, bromodeoxyuridine, interferons (IFNβ and IFNγ), and hydrogen peroxide. We analyzed senescence characteristics, colony formation ability, expression of genes involved in cell cycling and interferon signaling pathways, and protein levels. Treatment with all five agents decreased cell proliferation and induced cellular senescence in immortalized cholangiocyte and cholangiocarcinoma cell lines with different degrees of growth-inhibitory effects depending on cell type and origin. Bromodeoxyuridine gave the strongest stimulus to inhibit growth and induce senescence in most cell lines tested. Expression of p21 and interferon related genes was upregulated in most conditions. The fact that bromodeoxyuridine had the strongest effects on growth inhibition and senescence induction implies that senescence in cholangiocarcinoma cells is likely controlled by DNA damage response pathways relating to the p53/p21 signaling. In addition, interferon signaling pathways may partly regulate this mechanism in cholangiocarcinoma cells.
authors.affiliation: Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Bangkok, Thailand E-mail : benchamart@cri.or.th.
authors.forename: Benchamart
authors.initials: B
authors.lastname: Moolmuang
authors.forename: Pattama
authors.initials: P
authors.lastname: Singhirunnusorn
authors.forename: Mathuros
authors.initials: M
authors.lastname: Ruchirawat
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D016922:Cellular Senescence / Q000187:drug effects*; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D000077209:Decitabine; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007372:Interferons / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D000077209:Decitabine; D007372:Interferons; D006861:Hydrogen Peroxide; D001973:Bromodeoxyuridine; D001374:Azacitidine