DOI QR코드

DOI QR Code

Anti-cancer Activities of Ginseng Extract Fermented with Phellinus linteus

  • Lee, Jong-Jin (Department of Bioscience & Biotechnology, Central Research Center, Whanin Pharm. Co., Ltd.) ;
  • Kwon, Ho-Kyun (Department of Bioscience & Biotechnology, Central Research Center, Whanin Pharm. Co., Ltd.) ;
  • Jung, In-Ho (Department of Bioscience & Biotechnology, Central Research Center, Whanin Pharm. Co., Ltd.) ;
  • Cho, Yong-Baik (Department of Bioscience & Biotechnology, Central Research Center, Whanin Pharm. Co., Ltd.) ;
  • Kim, Kyu-Joong (Department of Biology, Kangnung National University) ;
  • Kim, Jong-Lae (Department of Bioscience & Biotechnology, Central Research Center, Whanin Pharm. Co., Ltd.)
  • Published : 2009.03.31

Abstract

In the present study, the anti-cancer effects of ginseng fermented with Phellinus linteus (GFPL) extract were examined through in vitro and in vivo assays. GFPL was produced by co-cultivating ginseng and Phellinus linteus together. Ginsenoside Rg3, Rh1 and Rh2 are important mediators of anti-angiogenesis and their levels in GFPL were enriched 24, 19 and 16 times, respectively, more than that of ginseng itself through the fermentation. GFPL exhibited distinct anti-cancer effects, including growth inhibition of the human lung carcinoma cell line A549, and promotion of immune activation by stimulating nitric oxide (NO) production in Raw 264.7 cells. Further evidence supporting anti-cancer effects of GFPL was its significant prolongment of the survival of B16F10 cancer cell-implanted mice. These results suggest that the GFPL may be a candidate for cancer prevention and treatment through immune activation and anti-angiogenic effects by enriching Rg3, Rh1 and Rh2.

Keywords

References

  1. Bikfalvi, A. and Bicknell, R. 2002. Recent advances in angiogenesis, antiangiosenesis and vascular targeting. Trends. Pharmacol. Sci. 23:576-582 https://doi.org/10.1016/S0165-6147(02)02109-0
  2. Bae, J., Jang, K., Yim, H. and Jin, H. 2005. Polysaccharides isolated from Phellinus gilvus inhibit melanoma growth in mice. Cancer Letter 218:43-52 https://doi.org/10.1016/j.canlet.2004.08.002
  3. Duan, W., Yu, Y. and Zhang, L. 2005. Antiatherogenic effects of Phyllantus Emblica associated with Corilagin and its Analogue. Yakugaku Zasshi 5:587-591
  4. Duerksen-Hughes, P. J., Day, D., Laster, S. M., Zachariades, N. A., Aquino, L. and Gooding, L. R. 1992. Both tumor necrosis factor and nitric oxide participate in lysis of simian virus 40-transformed cells by activated macrophages. J. Immunol. 149:2114-2122
  5. Folkman, J. 1995. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. 1:27-31 https://doi.org/10.1038/nm0195-27
  6. Folkman, J. 1974. Tumor Angiogenesis. Adv. Cancer Res. 19:331-358 https://doi.org/10.1016/S0065-230X(08)60058-5
  7. Han, S. B., Lee, C. W., Jeon, Y. J., Hong, N. D., Yoo, I. D., Yang, K. H. and Kim, H. M. 1999. The inhibitory effect of polysaccharide isolated from Phellinus linteus on tumor growth and metastasis. Immunopharmacol. 41:157-164 https://doi.org/10.1016/S0162-3109(98)00063-0
  8. Kiefer, D. and Pantuso, T. 2003. Panax ginseng. Am. Fam. Physician 68:1539-1542
  9. Kim, Y. C., Kim, S. R., Markelonis, G. J. and Oh, T. H. 1998. Ginsenosides Rb1 and Rg3 protect cultured rat cortical cells from glutamate-induced neurodegeneration. J. Neurosci. Res. 53:426-432 https://doi.org/10.1002/(SICI)1097-4547(19980815)53:4<426::AID-JNR4>3.0.CO;2-8
  10. Kim, M. W., Ko, S. R., Choi, K. J. and Kim, S. C. 1987. Distribution of saponin in various sections of Panax ginseng root and changes of its contens according to root age. Kor. J. Gineng Sci. 11:10-16
  11. Kim, J. L., Kwon, H. K., Chun, K. T., Kim, K. J. and Lee, K. K. 2000. Studies on cultural characteristics for high density fermentation of Phellinus linteus WI-001. Kor. J. Appl. Microbiol. Biotechnol. 28:105-110
  12. Kudo, K., Tachikawa, E., Kashimoto, T. and Takahashi, E. 1998. Properties of ginseng saponin inhibition of catecholamine secretion in bovine adrenal chromaffin cells. Eur. J. Phamacol. 341:139-144 https://doi.org/10.1016/S0014-2999(97)01350-2
  13. Liu, M. and Zhang, J. T. 1995. Protective effects of ginsenoside Rb1 and Rg1 on cultured hippocampal neurons. Yao Xue Xue Bao 30:674-678
  14. Lee, J. J., Kwon, H. K., Lee, D. S., Lee, S. W., Lee, K. K., Kim, K. J. and Kim, J. L. 2006. Mycelial extract of Phellinus linteus induces cell death in A549 lung cancer cells and elevation of NO in Raw 264.7 macrophage cells. Mycobiology 34:143-147 https://doi.org/10.4489/MYCO.2006.34.3.143
  15. Lowenstein, C. J., Dinerman, J. L. and Snyder, S. H. 1994. Nitric oxide: A physiologic messenger. Ann. Intern. Med. 120:227-237 https://doi.org/10.7326/0003-4819-120-3-199402010-00009
  16. Lorsbach, R. B., Murphy, W. J., Lowenstein, C. J., Snyder, S. H. and Russell, S. W. 1993. Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. J. Biol. Chem. 268:1908-1913
  17. Liekens, S., De Clercq, E. and Neyts, J. 2001. Angiogenesis: regulators and clinical applications. Biochem. Pharmacol. 61:253-270 https://doi.org/10.1016/S0006-2952(00)00529-3
  18. Mochizuki, M., Yoo, Y. C., Matsuzawa, K., Sato, K., Saiki, I. and Tonooka, S. 1995. Inhibitory effect of tumor metastasis in mice by saponins of red ginseng. Biol. Pharm. Bull. 18:1197-1202 https://doi.org/10.1248/bpb.18.1197
  19. Moncada, S., Palmer, R. M. and Higgs, E. A. 1991. Nitric oxide:physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 43:109-142
  20. Popovich, D. G. and Kitts, D. D. 2002. Structure-function relationship exists for ginsenosides in reducing cell proliferation and inducing apoptosis in the human leukemia (THP-1) cell line. Arch. Biochem. Biophys. 406:1-8 https://doi.org/10.1016/S0003-9861(02)00398-3
  21. Patrick, Y. K., Daisy, Y. L., Wu, P. K., Leung, P. Y. and Ricky, N. S. 2006. The angiosuppressive effects of 20®-ginsenoside Rg3. BioChem. Pharmacol. 72:437-445 https://doi.org/10.1016/j.bcp.2006.04.034
  22. Passaniti, A., Taylor, R. M., Pili, R., Guo, Y., Long, P. V., Haney, J. A., Pauly, R. R., Grant, D. S. and Martin, G. R. 1992. A simple, quantitative method for assessing angiogenesis and antiangiogenesis agents using reconstituted basement membrane, heparin and fibroblast growth factor. Lab. Invest. 67:519-528
  23. Pan, Z., Ye, D., Xie, X., Chen, H. and Lu, W. 2002. Antiangiogenesis of Rg3 in severe combined immunodeficient mice with human ovarian carcinoma. Zhonghua Fu Chan Ke Za Zhi. 37:227-230
  24. Puducalli, V. K. 2004. Inhibition of angiogenesis as a therapeutic strategy against brain tumors. Cancer Treat Res. 117:307-336
  25. Poderoso, J. J., Carreras, M. C., Schopfer, F., Lisdero, C. L., Riobo, N. A., Giulivi, C., Boveris, A. D., Boveris, A. and Cadenas, E. 1999. The reaction of nitric oxide with ubiquinol:kinetic properties and biological significance. Free Radic. Biol. Med. 26:925-935 https://doi.org/10.1016/S0891-5849(98)00277-9
  26. Stuehr, D. J. and Nathan, C. F. 1989. Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J. Exp. Med. 169:1543-1555 https://doi.org/10.1084/jem.169.5.1543
  27. Tonnesen, M. G., Feng, X. and Clark, R. A. 2000. Angiogenesis in wound healing. J. Investig Dermatol. Symp. Proc. 5:40-44 https://doi.org/10.1046/j.1087-0024.2000.00014.x
  28. Yun, T. K., Lee, Y. S., Lee, Y. H., Kim, S. I. and Yun, H. Y. 2001. Anticarcinogenic effect of Panax ginseng C A. Meyer and identification of active compounds. J. Korean Med. Sci. 16:S6-S18 https://doi.org/10.3346/jkms.2001.16.S.S6

Cited by

  1. Antiulcerogenic and Anticancer Activities of Korean Red Ginseng Extracts Bio-transformed by Paecilomyces tenuipes vol.57, pp.1, 2014, https://doi.org/10.3839/jabc.2014.007
  2. Neuroprotective effects of 20(S)-protopanaxadiol against glutamate-induced mitochondrial dysfunction in PC12 cells vol.37, pp.2, 2015, https://doi.org/10.3892/ijmm.2015.2440
  3. An AP2/ERF Family Transcription Factor PnERF1 Raised the Biosynthesis of Saponins in Panax notoginseng vol.36, pp.3, 2017, https://doi.org/10.1007/s00344-017-9672-z
  4. Ginseng on Cancer: Potential Role in Modulating Inflammation-Mediated Angiogenesis vol.45, pp.01, 2017, https://doi.org/10.1142/S0192415X17500021