Skip to main content

Advertisement

Log in

Anti-proliferative effects of ginsenosides extracted from mountain ginseng on lung cancer

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To investigate the effect of three major ginsenosides from mountain ginseng as anticancer substance and explore the underlying mechanism involved in lung cancer.

Methods

The inhibitory proliferation of lung cancer by major five ginsenosides (Rb1, Rb2, Rg1, Rc, and Re) was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Calculated 50% inhibition (IC50) values of five ginsenosides were determined and compared each other. Apoptosis by the treatment of single ginsenoside was performed by fluorescence-assisted cytometric spectroscopy. The alterations of apoptosis-related proteins were evaluated by Western blot analysis.

Results

The abundance of ginsenosides in butanol extract of mountain ginseng (BX-MG) was revealed in the order of Rb1, Rg1, Re, Rc and Rb2. Among them, Rb1 was the most effective to lung cancer cell, followed by Rb2 and Rg1 on the basis of relative IC50 values of IMR90 versus A549 cell. The alterations of apoptotic proteins were confirmed in lung cancer A549 cells according to the administration of Rb1, Rb2 and Rg1. The expression levels of caspase-3 and caspase-8 were increased upon the treatment of three ginsenosides, however, the levels of caspase-9 and anti-apoptotic protein Bax were not changed.

Conclusion

Major ginsenosides such as Rb1, Rb2 and Rg1 comprising BX-MG induced apoptosis in lung cancer cells via extrinsic apoptotic pathway rather than intrinsic mitochondrial pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Jia L, Zao YQ. Current evaluation of the millennium phytomedicine-ginseng (1): etymology, pharmacognosy, phytochemistry, market and regulations. Curr Med Chem 2009;16:2475–2484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Yun TK, Lee YS, Lee YH, Kim SI, Yun HY. Anticarcinogenic effect of Panax ginseng C. A. Meyer and identification of active compounds. J Kor Med Sci 2001;16(Suppl):S6–S18.

    Article  CAS  Google Scholar 

  3. Hu LY, Fan YP. Review of study on the mechanism of active ingredients of single Chinese drug in treating intracerebral hemorrhage. Chin J Integr Tradit West Med (Chin) 2006;26:376–380.

    CAS  Google Scholar 

  4. Han EJ, Kim YS, Yu KW, Jeong CS, Paek KY. Adventitious root cultures of Panax ginseng C. B. Meyer and ginsenoside production through large-scale bioreactor system. J Plant Biotech 2003;5:1–6.

    Google Scholar 

  5. Yoo BS, Chang MS, Byun SY. Characterization of cell cultures and ginsenoside production by cultured ginseng and wild mountain ginseng. Kor J Biotech Bioeng 2003;18:133–139.

    Google Scholar 

  6. Chang Y, Huang WJ, Tieen LT, Wang SJ. Ginsenosides Rg1 and Rb1 enhance glutamate release through activation of protein kinnase A in rat cerebrocortical nerve terminals (synaptosomes). Eur J Pharmacol 2008;578:28–36.

    Article  CAS  PubMed  Google Scholar 

  7. Chuang WC, Wu HK, Sheu SJ, Chiou SH, Chang HC, Chen YP. A comparative study on commercial samples of Rinseng radix. Planta Med 1995;61:459–465.

    Article  CAS  PubMed  Google Scholar 

  8. Wang CZ, Yuan CS. Potential role of ginseng in the treatment of colorectal cancer. Am J Chin Med 2008;36:1019–1028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Li BH, Wang CZ, He TC, Yuan CS, Du W. Antioxidants potentiate American ginseng-induced killing of colorectal cancer cells. Cancer Lett 2010;289:62–70.

    Article  CAS  PubMed  Google Scholar 

  10. Nakata H, Kikuchi Y, Tode T, Hirata J, Kita T, Ishii K, et al. Inhibitory effects of ginsenoside Rh2 on tumor growth in nude mice bearing human ovarian cancer cells. Cancer Sci 1998;89:733–740.

    CAS  Google Scholar 

  11. Oh M, Choi YH, Choi S, Chung H, Kim K, Kim SI,et al. Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells. Int J Oncol 1999;14:869–875.

    CAS  PubMed  Google Scholar 

  12. Wang CZ, Zhang B, Song WX, Wang A, Ni M, Luo X, et al. Steamed American ginseng berry: ginsenoside analyses and anticancer activities. J Agr Food Chem 2006;54:9936–9942.

    Article  CAS  Google Scholar 

  13. Zhang Q, Kang X, Zhao W. Antiangiogenic effect of lowdose cyclophosphamide combined with ginsenoside Rg3 on Lewis lung carcinoma. Biochim Biophys Res Comm 2006;342:824–828.

    Article  CAS  Google Scholar 

  14. Liu TG, Huang Y, Cui DD, Huang XB, Mao SH, Ji LL,et al. Inhibitory effect of ginsenoside Rg3 combined with gemcitabine on angiogenesis and growth of lung cancer in mice. BMC Cancer 2009;23:250.

    Article  Google Scholar 

  15. Lu P, Su W, Miao ZH, Niu HR, Liu J, Hua QL. Effect and mechanism of ginsenoside Rg3 on postoperative life span of patients with non-small cell lung cancer. Chin J Integr Med 2008;14:33–36.

    Article  CAS  PubMed  Google Scholar 

  16. Hwang JW, Oh JH, Yoo HS, Lee YW, Cho CK, Kwo KR,et al. Mountain ginseng extract exhibits anti-lung cancer activity by inhibiting the nuclear translocation of NF-κB. Am J Chin Med 2012;40:187–202.

    Article  CAS  PubMed  Google Scholar 

  17. Al HH, Wheatley-Price P, Clemons M, Shepherd FA. Prevention and management of bone metastases in lung cancer: a review. J Thorac Oncol 2009;4:251–259.

    Article  Google Scholar 

  18. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics. CA Cancer J Clin 2009;59:225–249.

    Article  PubMed  Google Scholar 

  19. Lee JH, Kwon KR, Cho CK, Han SS, Yoo HS. Advanced cancer cases treated with cultivated wild ginseng pharmacopuncture. J Acupunct Meridi Stud 2010;3:119–124.

    Article  CAS  Google Scholar 

  20. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth 1983;65:55–63.

    Article  CAS  Google Scholar 

  21. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pahrmacol 1999;58:1685–1693.

    Article  CAS  Google Scholar 

  22. Gillis CN. Panax ginseng pharmacology: a nitric oxide link? Biochem Pharmacol 1997;54:1–8.

    Article  CAS  PubMed  Google Scholar 

  23. Shin HR, Kim JY, Yun TK, Morgan G, Vainio H. The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes Control 2000;11:565–576.

    Article  CAS  PubMed  Google Scholar 

  24. Koo HN, Jeong HJ, Choi IY, An HJ, Moon PD, Kim SJ,et al. Mountain grown ginseng induces apoptosis in HL-60 cells and its mechanism have little relation with TNF-alpha production. Am J Chin Med 2007;35:169–182.

    Article  PubMed  Google Scholar 

  25. Qi LW, Wang CZ, Yuan CS. American ginseng: potential structure-function relationship in cancer chemoprevention. Biochem Pharmacol 2010;80:947–954.

    Article  CAS  PubMed  Google Scholar 

  26. Sato K, Mochizuki M, Saiki I, Yoo YC, Samukawa K, Azuma I. Inhibition of tumor angiogenesis and metastasis by a saponin of Panax ginseng, ginsenoside-Rb2. Biol Pharm Bull 1994;17:635–639.

    Article  CAS  PubMed  Google Scholar 

  27. Shinkai K, Akedo H, Mukai M, Imamura F, Isoai A, Kobayashi M, et al. Inhibition of in vitro tumor cell invasion by ginsenoside Rg3. Jpn K Cancer Res 1996;87:357–362.

    Article  CAS  Google Scholar 

  28. Cheng CC, Yang SM, Huang CY, Chen JC, Chang WM, Hsu SL. Molecular mechanisms of ginsenoside Rh2-mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells. Cancer Chemother Pharmacol 2005;55:531–540.

    Article  CAS  PubMed  Google Scholar 

  29. Chen MW, Ni L, Zhao XG, Niu XY. The inhibition of 20(R)-ginsenoside Rg3 on the expression of angiogenesis factors proteins in human lung carcinoma cell line A549 and HUVEC304 cell. Chin J Mater Med (Chin) 2005;30:357–360.

    CAS  Google Scholar 

  30. Wang W, Rayburn ER, Hang J, Zhao Y, Wang H, Zhang R. Anti-lung cancer effects of novel ginsenoside 25-OCH(3)-PPD. Lung Cancer 2009;65:306–311.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Mohamad N, Gutiérrez A, Núñez M, Cocca C, Martín G, Cricco G, et al. Mitochondrial apoptotic pathways. Biocell 2005;29:149–161.

    CAS  PubMed  Google Scholar 

  32. Cho SH, Chung KS, Choi JH, Kim DH, Lee KT. Compound K, a metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells. BMC Cancer 2009;9:449.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hyun Joo An or Jong-Soon Choi.

Additional information

Equally contributed to this work

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, D.G., Jang, SI., Kim, YR. et al. Anti-proliferative effects of ginsenosides extracted from mountain ginseng on lung cancer. Chin. J. Integr. Med. 22, 344–352 (2016). https://doi.org/10.1007/s11655-014-1789-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-014-1789-8

Keywords

Navigation