Mechanism of Apoptosis Induced by Ursolic Acid in Gastric Carcinoma BGC-823 Cells

Objective: To investigate ursolic acid(UA) proliferation inhibiting and apoptosis inducing effect on human gastric carcinoma cell line BGC-823.Methods: Cell proliferation inhibition was detected by MTT assay.DNA fragmentation was determined by DNA electrophoresis.Cell cycle and apoptosis rate were analyzed by flow cytometry(FCM).Fas antigen expression on BGC-823 cell surface was detected with Fas monoclonal antibody and then analyzed by FCM.The expression of Bcl-2 and activity of caspase-8 and -3 were detected by Western blot.Results: UA can inhibit proliferation of BGC-823 cells effectively in a dose- and time-dependent manner.After BGC-823 was treated by UA for 24 h,the IC_(50) value was 43.10 μmol/L.When UA concentration was 50 or 60 μmol/L,DNA ladder of apoptosis was observed by gel electrophoresis.While UA concentration was increased from 20 μmol/L to 60 μmol/L,cells in sub-G_(1) phase and S-phase were increased in cell cycle,but decreased in G_(1)-phase.UA decreased Bcl-2 protein levels and increased the activation of caspase-3 and caspase-8.The Fas expression on BGC-823 cells was not found.(Conclusion:) UA has inhibitory and apoptosis inducing effects on BGC-823 cells.Down-regulation of the expression of Bcl-2 and induction of activation of caspase-8 and -3 may contribute to its apoptosis effects.