American ginseng berry enhances chemopreventive effect of 5-FU on human colorectal cancer cells

Abstract

Abstract. 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 antiproliferative 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 concentrationdependent 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. IntroductionColorectal cancer is one of the most common malignancies and ranks as the second greatest cause of cancer death in both men and women worldwide (1). Although early stage colorectal cancer can be cured by surgical resection, surgery is often combined with adjuvant radiotherapy and chemotherapy with one or more chemotherapeutic agents. Even with effective strategies that continue to be developed for treating colorectal cancer, chemotherapy has the drawbacks of severe adverse effects and dose-limiting toxicity. Drug-related adverse events not only worsen patients' quality of life, but can also lead to their refusal to continue chemotherapy (2,3). Chemotherapy-induced toxicity can be reduced by chemoadjuvant compounds that potentiate tumoricidal effects with lower doses (4-6). Identifying non-toxic chemo-adjuvants among herbal medicines may be an essential step in advancing the treatment of cancer (7).Due to the increase in the consumption of herbal remedies in the United States along with a staggering popularity of the ginseng herb as a method of sustaining good health, significant focus has been placed on American ginseng (Panax quinquefolius L.) (8), which belongs to the genus Panax L. in the Araliaceae family. American ginseng has been reported to ...

Herbal compound "Songyou Yin" reinforced the ability of interferon-alfa to inhibit the enhanced metastatic potential induced by palliative resection of hepatocellular carcinoma in nude mice

“…Our previous studies revealed that IFN-α inhibited HCC and extended the lifespan of mice and could be attributed to anti-angiogenesis [14,16]; SYY directly down-regulated MMP2 and VEGF and inhibited HCC growth and metastasis [15]. Others also reported that herbal medicine could inhibit the growth of MHCC97H cells used in this study [27] and could inhibit the invasiveness potential of HCC cells via MMP2 inhibition [28]. Based on our in vitro and in vivo studies, we considered that inhibition of the metastasis-enhancing effects due to dysregulation of MMP2/TIMP2 and VEGF might further improve operative efficacy in patients with HCC.…”