Effect of 3,3′-Biisofraxidin on Apoptosis of Human Gastric Cancer BGC-823 Cells

Purpose: To study the effect of 3,3′-biisofraxidin from Sarcandrae Herba on the proliferation of BGC- 823 cells and the possible mechanisms.Methods: Cell Counting Kit-8 (CCK-8), flow cytometry, Western blot and xenograft assays were used to determine the effects of 3,3′-biisofraxidin on the proliferation, apoptosis, apoptotic proteins and xenograft of BGC-823 cells.Results: 3,3′-Biisofraxidin significantly (p < 0.01) inhibited the proliferation of BGC-823 cells (concentrations: 10 - 40 μM; cell viability: 30.45 - 76.68 % in CCK-8 assay) with half maximal inhibitory concentration (IC50) value of 20.35 μM and induced the apoptosis of BGC-823 cells (concentrations: 10, 20 and 40 μM; apoptotic cells: 11.92, 20.10 and 33.64 % in flow cytometry assay), compared with the control (cell viability: 99.73 %; apoptotic cells: 5.18 %). 3,3′-Biisofraxidin (10, 20 and 40 μM in vitro; 40 mg/kg in vivo) significantly (p < 0.05 or 0.01) down-regulated the expressions of anti-apoptotic proteins (Bcl-2, Bcl-xl and Survivin) and up-regulated the expressions of pro-apoptotic proteins (Smac, caspase-3, caspase-7 and caspase-9), compared with the control. Moreover, the release of cytochrome c from the mitochondria to the cytoplasm was significantly (p < 0.01) promoted in vitro, compared with the control. 3,3′-Biisofraxidin (40 mg/kg) significantly (p < 0.05 or 0.01) inhibited the growth of tumor in xenograft assay, compared with the control.Conclusion: 3,3′-Biisofraxidin significantly induces the apoptosis of BGC-823 cells in vitro and in vivo through the mitochondria-mediated apoptotic pathway, and therefore has a potential to be developed into an anti-gastric cancer drug.Keywords: Sarcandrae Herba, Gastric cancer, 3,3′-Biisofraxidin, Mitochondria-mediated apoptotsis, Cell Counting Kit-8, Xenograft