Jian-Tao Wu1,2 ,
She-Min Lv1,
Chun-Hui Lu1,
Jun Gong1,
Jian-Bo An3
1School of Medicine, Xi'an Jiaotong University, Xi'an 710000;
2Shaanxi University of Chinese Medicine, Xi'an 710000;
3Xi'an Center for Diseases Control and Prevention, Xi'an 710000, PR China.
For correspondence:- Jian-Tao Wu
Email: jtwu_xa@163.com
Received: 11 May 2015
Accepted: 1 September 2015
Published: 31 October 2015
Citation:
Wu J, Lv S, Lu C, Gong J, An J.
Effect of 3,3'-biisofraxidin on apoptosis of human gastric cancer BGC-823 cells. Trop J Pharm Res 2015; 14(10):1803-1811
doi:
10.4314/tjpr.v14i10.10
© 2015 The authors.
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Abstract
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, 3,3R42;-Biisofraxidin, Mitochondria-mediated apoptotsis, Cell Counting Kit-8, Xenograft