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

被引:62
作者
Chih, HW
Chiu, HF [1 ]
Tang, KS
Chang, FR
Wu, YC
机构
[1] Fooyin Inst Technol, Kaohsiung 831, Taiwan
[2] Kaohsiung Med Univ, Dept Pharmacol, Kaohsiung 807, Taiwan
[3] Kaohsiung Med Univ, Grad Inst Nat Prod, Kaohsiung 807, Taiwan
关键词
acetogenin; bullatacin; apoptosis; hepatocarcinoma;
D O I
10.1016/S0024-3205(01)01209-7
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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. [H-3]-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). (C) 2001 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:1321 / 1331
页数:11
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