Bullatacin, a potent antitumor annonaceous acetogenin, inhibits proliferation of human hepatocarcinoma cell line 2.2.15 by apoptosis induction

Bullatacin, isolated from the fruit of Annona atemoya, is one of the most p otentially effective antitumor annonaceous acetogenins. Bullatacin was stud ied here for its ability to inhibit the proliferation of 2.2.15 cells, hepa titis 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 expo sure to bullatacin were 7.8 +/- 2.5 nM for 2.2.15 cells. [H-3]-Thymidine in corporation assays showed almost the same results. Bullatacin-treatment als o reduced concentrations of hepatitis B surface antigen (HBsAg) in the cult ured 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 reveal ed 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 fl uorescein-isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI) . (C) 2001 Elsevier Science Inc. All rights reserved.