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Previous studies showed that Asian ginseng, Panax ginseng C.A. Meyer, may have anti-cancer properties. However, there is limited data exploring the use of Asian ginseng as an adjuvant to chemotherapy, and minimal mechanistic studies related to their possible synergistic activities. In this study, the content of 8 ginsenosides, Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1 and Rg3, in the extracts of white ginseng (WG) and red ginseng (RG) were determined by HPLC. Using HCT-116 human colorectal cancer cells, we compared the efficacy of WG and RG. We evaluated the synergy between ginseng and 5-fluorouracil (5-FU), and explored the mechanism of their anti-proliferative effects. As single extract, WG or RG used at concentrations of 0.1, 0.2 and 0.3 mg/mL, inhibited HCT-116 cell proliferation in a concentration-related manner. WG at 0.2 mg/mL did not show obvious synergy with 5-FU co-treatment, while RG at 0.2 and 0.3 mg/mL significantly enhanced the anti-proliferative effects of 5-FU at concentrations of 10, 50 and 100 microM (P < 0.05). Using flow cytometric assay, RG 0.3 mg/mL did not affect cancer cell apoptotic induction activity. However, the RG induced cell cycle arrest in the G1 phase, while 5-FU arrested the cell in the S phase. Different ginsenoside profiles are responsible for the observed differences in pharmacological effects. The effects of 8 ginsenosides on HCT-116 cells were assayed. Rd and Rg3 showed positive anti-proliferative effect. Our data suggested a potential for RG as an adjuvant therapy in the treatment of colorectal cancer, via a synergistic action.

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Human colorectal cancer is a common malignancy with a 2008 recorded incidence of 148810 cases with a mortality of 49960 in the United States alone. 1) Half of all patients diagnosed with colorectal cancer eventually will die from the disease; and only less than 10% of patients with metastatic colorectal cancer will survive more than five years after diagnosis. Although many early stage colorectal cancers are cured by surgical resection alone, most often, surgery is combined with adjuvant radio-and chemotherapy. Patients treated for advanced staged colorectal cancer with adjuvant chemotherapy showed a reduced risk of relapse.2) However, commonly used chemotherapy has the drawbacks of severe adverse effects and dose-limiting toxicity. The drug-related adverse effects not only worsen patients' quality of life, but can also lead to their refusal to continue the potentially curative chemotherapy.3,4) Therefore, the need for the identification of non-toxic chemo-adjuvant treatments from herbal medicines remains an essential goal to advance cancer therapeutics.Asian ginseng (Panax ginseng C. A. MEYER) has been used for thousands of years. 5,6) The known biochemical and pharmacological effects of ginseng are antiaging, antidiabetic, anticarcinogenic, and antifatique, along with promotion of DNA, RNA and protein synthesis. [7][8][9] In oriental countries, Asian ginseng root can be steamed to produce red ginseng, the pharmacological effects, such as the anticancer activity, of red ginseng are stronger than that of unsteamed ginseng. 10,11) Another species in the Panax genus, American ginseng (Panax quinquefolius L.), has gained popularity with the American public in the past decade, 7,12) however since most studies have focused on the root of Asian ginseng, there is limited data available with regard to the cancer preventive potential of American ginseng.We evaluated the cancer chemopreventive activities of American ginseng root extract on human colorectal and breast cancer. 11,13) It is believed that the bioactive constituents in American ginseng are ginsenosides. Ginsenosides are distributed in many parts of the plant, including the root, leaf and berry. The different parts of the plant contain distinct ginsenoside profiles, 7,14) and because of this, they may possess different pharmacological activities. Since the root is the most commonly used part of American ginseng, the potential cancer preventive qualities of other parts, such as the berry, has yet to be explored. In a recent pilot study, we observed that steaming the American ginseng berry changed its chemical composition.15) However, the anticancer effects of ginseng berry have not been systematically studied, and observed in vivo. In addition, the effects of heat treatment on the ginsenoside content of ginseng berry extract have not been determined.The aims of this study were to compare the chemical differences between unsteamed American ginseng berry extract (AGE) and steamed American ginseng berry extract (S-AGE) and to investigate the chemopreventive effects...