Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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).
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PMID:Bullatacin, a potent antitumor annonaceous acetogenin, inhibits proliferation of human hepatocarcinoma cell line 2.2.15 by apoptosis induction. 1152 56

Bullatacin, a potential antitumor Annonaceous acetogenin (AA), is isolated from the seed of the Formosa Annona atemoya. We reported previously that bullatacin inhibits the secretion of hepatitis B surface antigen from 2.2.15 cells (human hepatoma HepG2 cells transfected with hepatitis B virus DNA plasmid). In the present study, we determined cell apoptosis by using double-dye staining with fluorescein-isothiocyanate-labeled annexin V and propidium iodide. We found that bullatacin induced apoptosis in 2.2.15 cells in a time-dependent manner; the most significant apoptotic change appeared at 16 hr. Moreover, different concentrations (10(-3) to 1.0 microM) of bullatacin induced apoptosis in a concentration-dependent manner at 16 hr. The determination of intracellular cyclic AMP (cAMP) and cyclic GMP (cGMP) levels in 2.2.15 cells after exposure to bullatacin demonstrated that bullatacin caused both to decrease in a time- and concentration-dependent manner. A time course (0.33, 1, 6, 16, 24hr) study indicated that while both cAMP and cGMP levels decreased early (at 0.33 hr), the most dramatic decline appeared at 6 hr. Meanwhile, the inhibitory effect on cAMP and cGMP levels reached a maximum at 16 hr (90.5+/-3.2 and 47.3+/-12.8%, respectively). The concentration-dependent decrease of both cAMP and cGMP induced by bullatacin was parallel with the magnitude of apoptosis induced by various concentrations (10(-3) to 1.0 microM) of bullatacin. Additionally, the bullatacin-induced apoptosis was inhibited by the addition of cAMP and cGMP elevating agents (forskolin and S-nitrosoglutathione). Our results suggest that a decrease of both cAMP and cGMP levels may play a crucial role in bullatacin-induced apoptosis in 2.2.15 cells.
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PMID:Bullatacin, a potent antitumor Annonaceous acetogenin, induces apoptosis through a reduction of intracellular cAMP and cGMP levels in human hepatoma 2.2.15 cells. 1252 25