title: Bullatacin, a potent antitumor annonaceous acetogenin, inhibits proliferation of human hepatocarcinoma cell line 2.2.15 by apoptosis induction.
abstract: Bullatacin, isolated from the fruit of Annona atemoya, is one of the most potentially effective antitumor annonaceous acetogenins. Bullatacin was studied here for its ability to inhibit the proliferation of 2.2.15 cells, hepatitis B virus (HBV) DNA transfected human hepatocarcinoma cell line. It was found that bullatacin induced cytotoxicity of 2.2.15 cells in a time- and dose-dependent manner. Fifty percent effective dose (ED50) on day 1 of exposure to bullatacin were 7.8 +/- 2.5 nM for 2.2.15 cells. [3H]-Thymidine incorporation assays showed almost the same results. Bullatacin-treatment also reduced concentrations of hepatitis B surface antigen (HBsAg) in the cultured medium released from 2.2.15 cells, coincident with the decrease in the cell proliferation. Analysis of mophological changes of bullatacin-treated 2.2.15 by inverted phase-contrast microscope and eletron microscopy revealed a possible model of action for bullatacin to inhibit proliferation of 2.2.15 cells by inducing apoptosis. Most of the bullatacin-induced cell death was found to be due to apoptosis, as determined by double staining with fluorescein-isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI).
authors.affiliation: Fooyin Institute of Technology, Kaohsiung County, Taiwan, ROC.
authors.forename: H W
authors.initials: HW
authors.lastname: Chih
authors.forename: H F
authors.initials: HF
authors.lastname: Chiu
authors.forename: K S
authors.initials: KS
authors.lastname: Tang
authors.forename: F R
authors.initials: FR
authors.lastname: Chang
authors.forename: Y C
authors.initials: YC
authors.lastname: Wu
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005362:Ficoll / Q000031:analogs & derivatives / Q000378:metabolism; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D005663:Furans / Q000494:pharmacology* / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology*; D011419:Propidium / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000473:pathology
chemical_list: D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic; D017077:Culture Media, Conditioned; D005663:Furans; D006514:Hepatitis B Surface Antigens; C045540:fluorescein 5-isothiocyanate-Ficoll; C061022:bullatacin; D005362:Ficoll; D011419:Propidium; D004247:DNA; D016650:Fluorescein-5-isothiocyanate