In this study, we investigated the possible synergistic chemopreventive effects of American ginseng berry extract (AGBE) and 5-fluorouracil (5-FU) on human colorectal cancer cell lines, SW-480, HCT-116 and HT-29. We used high-performance liquid chromatography to determine the contents of major ginsenosides, the active components of American ginseng, in AGBE. The anti-proliferative effects were evaluated by the cell counting method. AGBE (0.1-1.0 mg/ml) significantly inhibited SW-480, HCT-116 and HT-29 cell growth in a concentration-dependent manner. Cell growth decreased more with the combined treatment of 5-FU and AGBE than with 5-FU or AGBE applied alone, suggesting that AGBE can reduce the dose of 5-FU needed to achieve desired effects and thereby decrease the dose-related toxicity of the chemotherapy agent. Cell apoptosis assay showed that AGBE markedly reduced the number of viable SW-480 cells at 0.5 and 1.0 mg/ml, but did not increase cell apoptosis significantly. Neither 5-FU nor co-treatment with 5-FU and AGBE induced cell apoptosis markedly. Cell cycle assay showed that AGBE mainly arrested SW-480 cells in the G2/M phase. 5-FU increased the percentage of SW-480 cells at the S phase of the cell cycle. The assay of combined treatment groups indicated that AGBE can heighten the arrest of SW-480 cells in the S phase induced by 5-FU, and increase the cell distribution in G2/M phase compared with 5-FU applied alone. The trend of increasing cyclin A was similar to the increase of S and G2/M phase cells in all treated groups. The enhancement of S and G2/M phase arrest, rather than cell apoptosis, should be the mechanism of synergistic effects of AGBE on 5-FU. Further in vivo and clinical trials are needed to test AGBE as a valuable chemo-adjuvant.

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