|American ginseng berry enhances chemopreventive effect of 5-FU on human colorectal cancer cells|
Authors: Xiao-Li Li, Chong-Zhi Wang, Shi Sun, Sangeeta R. Mehendale, Wei Du, Tong-Chuan He, Chun-Su Yuan
Tang Center for Herbal Medicine Research and Department of Anesthesia and Critical Care, The Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA
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.