The Chinese medicine Bu-Zhong-Yi-Qi-Tang inhibited proliferation of hepatoma cell lines by inducing apoptosis via G0/G1 arrest

Bu-Zhong-Yi-Qi-Tang (BZYQT), a Chinese herbal medicine, inhibited the proli feration of human hepatoma cell lines (Hep3B, HepG2 and HA22T) dose-depende ntly, The IC50s of BZYQT on the proliferation of Hep3B, HepG2 and HA22T wer e 432.5 +/- 31.8 mug/ml, 455.4 +/- 24.2 mug/ml, and 2284.3 +/- 77.2 mug/ml respectively on day 3. However, BZYQT did not significantly inhibit the pro liferation of normal human hepatocytes (Chang liver, CCL-13) at the concent ration under 5,000 mug/ml. Major compounds of BZYQT, including astragalosid e IV, ginsenoside Rb1 and Rg1, saikosaponin a and c, and glycyrrhizin, have been identified. To investigate the key inhibitors of BZYQT, Hep3B cells w ere treated with BZYQT, individual major compounds of BZYQT. and mixture of major compounds in the same ratio as present in BZYQT. Significant inhibit ion of proliferation was detected in BZYQT and its major compounds mixture in a comparable level. Not any individual major compound examined could sup press the proliferation of Hep3B cells. This data indicated that there coul d be synergistic or additive effects of the ingredients in BZYQT. BrdU inco rporation. cell cycle analysis and DNA fragmentation assay revealed that BZ YQT suppressed the proliferation of hepatoma cells via G0/G1 cell cycle arr est and inhibition of DNA synthesis followed by apoptosis. (C) 2001 Elsevie r Science Inc. All rights reserved.