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Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells

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Abstract

Purpose

Panax notoginseng is a commonly used Chinese herb. Although a few studies have found that notoginseng shows anti-tumor effects, the effect of this herb on colorectal cancer cells has not been investigated. 5-Fluorouracil (5-FU) is a chemotherapeutic agent for the treatment of colorectal cancer that interferes with the growth of cancer cells. However, this compound has serious side effects at high doses. In this study, using HCT-116 human colorectal cancer cell line, we investigated the possible synergistic anti-cancer effects between notoginseng flower extract (NGF) and 5-FU on colon cancer cells.

Methods

The anti-proliferation activity of these modes of treatment was evaluated by MTS cell proliferation assay. Apoptotic effects were analyzed by using Hoechst 33258 staining and Annexin-V/PI staining assays. The anti-proliferation effects of four major single compounds from NGF, ginsenosides Rb1, Rb3, Rc and Rg3 were also analyzed.

Results

Both 5-FU and NGF inhibited proliferation of HCT-116 cells. With increasing doses of 5-FU, the anti-proliferation effect was slowly increased. The combined usage of 5-FU 5 μM and NGF 0.25 mg/ml, significantly increased the anti-proliferation effect (59.4 ± 3.3%) compared with using the two medicines separately (5-FU 5 μM, 31.1 ± 0.4%; NGF 0.25 mg/ml, 25.3 ± 3.6%). Apoptotic analysis showed that at this concentration, 5-FU did not exert an apoptotic effect, while apoptotic cells induced by NGF were observed, suggesting that the anti-proliferation target(s) of NGF may be different from that of 5-FU, which is known to inhibit thymidilate synthase.

Conclusions

This study demonstrates that NGF can enhance the anti-proliferation effect of 5-FU on HCT-116 human colorectal cancer cells and may decrease the dosage of 5-FU needed for colorectal cancer treatment.

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Acknowledgments

This work was supported in part by research grants from the American Cancer Society (RSG-05-254–01DDC), the NIH/NCI (1RO1 CA106569-01), and the NIH/NCCAM (AT002176 and AT002445).

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Authors and Affiliations

  1. Tang Center for Herbal Medicine Research, The University of Chicago, 5841 South Maryland Avenue, MC 4028, Chicago, IL, 60637, USA

    Chong-Zhi Wang, Ming Ni, Sangeeta Mehendale, Jing-Tian Xie, Han H. Aung & Chun-Su Yuan

  2. Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL, 60637, USA

    Chong-Zhi Wang, Ming Ni, Sangeeta Mehendale, Jing-Tian Xie, Han H. Aung & Chun-Su Yuan

  3. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, IL, 60637, USA

    Xiaoji Luo, Wen-Xin Song & Tong-Chuan He

  4. Committee on Immunology and Department of Pathology, The University of Chicago, Chicago, IL, 60637, USA

    Bin Zhang

  5. Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL, 60637, USA

    Chun-Su Yuan

Authors
  1. Chong-Zhi Wang
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  2. Xiaoji Luo
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  3. Bin Zhang
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  4. Wen-Xin Song
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  5. Ming Ni
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  6. Sangeeta Mehendale
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  7. Jing-Tian Xie
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  8. Han H. Aung
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  9. Tong-Chuan He
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  10. Chun-Su Yuan
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Corresponding author

Correspondence to Chun-Su Yuan.

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Wang, CZ., Luo, X., Zhang, B. et al. Notoginseng enhances anti-cancer effect of 5-fluorouracil on human colorectal cancer cells. Cancer Chemother Pharmacol 60, 69–79 (2007). https://doi.org/10.1007/s00280-006-0350-2

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  • DOI: https://doi.org/10.1007/s00280-006-0350-2

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