title: The cytotoxic effects of bile acids in crude bile on human pancreatic cancer cell lines.
abstract: Pancreatic cancer frequently causes extrahepatic cholestasis. To identify the direct effects of bile acids in jaundiced serum on pancreatic cancer, the proliferation of PANC-1 and MIA PaCa-2 cells as well as the ultrastructural alteration of PANC-1 cells cultured in crude bile modified media were studied. The growth of these cells in the RPMI-1640 media with or without 1%, 2%, and 4% of the refined crude bile was assessed after 48 and 96 h of incubation. The ultrastructure of PANC-1 cells was investigated by scanning and transmission electron microscopy after 24 and 48 h of incubation. The proliferation of both cell lines in the bile-treated media was greatly inhibited. The inhibitory rates of bile on PANC-1 ranged from 24.1% +/- 3.3% to 66.9% +/- 6.6% (P < 0.01) and those on MIA PaCa-2 ranged from 16.7% +/- 3.8% to 50.7% +/- 5.5%. (P < 0.01). When the bile-added media were replaced, the cells were able to restore their proliferating ability. The PANC-1 cells incubated in the bile-supplied media indicated that the mirovilli, mitochondria, and other organelles had thus been injured. These results suggest that bile acids appear to inhibit the proliferation of PANC-1 and MIA PaCa-2 cells, and the probable inhibitory mechanism is mainly considered to be due to the cytotoxicity of such bile acids.
authors.affiliation: First Department of Surgery, Nippon Medical School, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: Onda
authors.forename: E
authors.initials: E
authors.lastname: Uchida
authors.forename: S
authors.initials: S
authors.lastname: Yamamura
authors.forename: K
authors.initials: K
authors.lastname: Yanagi
authors.forename: A
authors.initials: A
authors.lastname: Matsushita
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Fukuhara
authors.forename: K
authors.initials: K
authors.lastname: Aida
authors.forename: T
authors.initials: T
authors.lastname: Tajiri
mesh_terms: D001647:Bile Acids and Salts / Q000378:metabolism*; D002455:Cell Division; D001651:Cholestasis, Extrahepatic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned; D003603:Cytotoxins / Q000378:metabolism*; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D017077:Culture Media, Conditioned; D003603:Cytotoxins; D006131:Growth Inhibitors