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Bullatacin, a potent antitumor annonaceous acetogenin, inhibits proliferation of human hepatocarcinoma cell line 2.2.15 by apoptosis induction.
- Source :
-
Life sciences [Life Sci] 2001 Aug 03; Vol. 69 (11), pp. 1321-31. - Publication Year :
- 2001
-
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).
- Subjects :
- Annexin A5 metabolism
Antineoplastic Agents, Phytogenic therapeutic use
Carcinoma, Hepatocellular drug therapy
Cell Death drug effects
Cell Division drug effects
Culture Media, Conditioned metabolism
DNA biosynthesis
DNA drug effects
Dose-Response Relationship, Drug
Ficoll analogs & derivatives
Ficoll metabolism
Flow Cytometry
Fluorescein-5-isothiocyanate analogs & derivatives
Fluorescein-5-isothiocyanate metabolism
Furans therapeutic use
Hepatitis B Surface Antigens metabolism
Humans
Liver Neoplasms drug therapy
Propidium metabolism
Tumor Cells, Cultured cytology
Tumor Cells, Cultured drug effects
Tumor Cells, Cultured pathology
Antineoplastic Agents, Phytogenic pharmacology
Apoptosis drug effects
Carcinoma, Hepatocellular pathology
Furans pharmacology
Liver Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0024-3205
- Volume :
- 69
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 11521756
- Full Text :
- https://doi.org/10.1016/s0024-3205(01)01209-7