Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Comparison of anticancer activities of Korean Red Ginseng-derived fractions

  • Baek, Kwang-Soo (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Yi, Young-Su (Department of Pharmaceutical Engineering, Cheongju University) ;
  • Son, Young-Jin (Department of Pharmacy, Sunchon National University) ;
  • Jeong, Deok (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Sung, Nak Yoon (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Aravinthan, Adithan (Department of Physiology, College of Veterinary Medicine, Chonbuk National University) ;
  • Kim, Jong-Hoon (Department of Physiology, College of Veterinary Medicine, Chonbuk National University) ;
  • Cho, Jae Youl (Department of Genetic Engineering, Sungkyunkwan University)
  • Received : 2016.09.08
  • Accepted : 2016.11.07
  • Published : 2017.07.15
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Abstract

Background: Korean Red Ginseng (KRG) is an ethnopharmacological plant that is traditionally used to improve the body's immune functions and ameliorate the symptoms of various diseases. However, the antitumorigenic effects of KRG and its underlying molecular and cellular mechanisms are not fully understood in terms of its individual components. In this study, in vitro and in vivo antitumorigenic activities of KRG were explored in water extract (WE), saponin fraction (SF), and nonsaponin fraction (NSF). Methods: In vitro antitumorigenic activities of WE, SF, and NSF of KRG were investigated in the C6 glioma cell line using cytotoxicity, migration, and proliferation assays. The underlying molecular mechanisms of KRG fractions were determined by examining the signaling cascades of apoptotic cell death by semiquantitative reverse transcriptase polymerase chain reaction and Western blot analysis. The in vivo antitumorigenic activities of WE, SF, and NSF were investigated in a xenograft mouse model. Results: SF induced apoptotic death of C6 glioma cells and suppressed migration and proliferation of C6 glioma cells, whereas WE and NSF neither induced apoptosis nor suppressed migration of C6 glioma cells. SF downregulated the expression of the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2) and upregulated the expression of the pro-apoptotic gene Bcl-2-associated X protein (BAX) in C6 glioma cells but had no effect on the expression of the p53 tumor-suppressor gene. Moreover, SF treatment resulted in activation of caspase-3 as evidenced by increased levels of cleaved caspase-3. Finally, WE, SF, and NSF exhibited in vivo antitumorigenic activities in the xenograft mouse model by suppressing the growth of grafted CT-26 carcinoma cells without decreasing the animal body weight. Conclusion: These results suggest that WE, SF, and NSF of KRG are able to suppress tumor growth via different molecular and cellular mechanisms, including induction of apoptosis and activation of immune cells.

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References

  1. Rhee MY, Cho B, Kim KI, Kim J, Kim MK, Lee EK, Kim HJ, Kim CH. Blood pressure lowering effect of Korea ginseng derived ginseol K-g1. Am J Chin Med 2014;42:605-18. https://doi.org/10.1142/S0192415X14500396
  2. Wang CZ, Mehendale SR, Yuan CS. Commonly used antioxidant botanicals: active constituents and their potential role in cardiovascular illness. Am J Chin Med 2007;35:543-58. https://doi.org/10.1142/S0192415X07005053
  3. Leggett S, Koczwara B, Miller M. The impact of complementary and alternative medicines on cancer symptoms, treatment side effects, quality of life, and survival in women with breast cancerea systematic review. Nutr Cancer 2015;67:373-91. https://doi.org/10.1080/01635581.2015.1004731
  4. Han YS, Lee JH, Lee SH. Antitumor effects of fucoidan on human colon cancer cells via activation of Akt signaling. Biomol Ther (Seoul) 2015;23:225-32. https://doi.org/10.4062/biomolther.2014.136
  5. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA 2001;286:208-16. https://doi.org/10.1001/jama.286.2.208
  6. Kim MS, Lee Y, Sung GH, Kim JH, Park JG, Kim HG, Baek KS, Cho JH, Han J, Lee KH, et al. Pro-apoptotic activity of 4-isopropyl-2-(1-phenylethyl) aniline isolated from Cordyceps bassiana. Biomol Ther (Seoul) 2015;23:367-73. https://doi.org/10.4062/biomolther.2015.021
  7. Yuan CS, Wei G, Dey L, Karrison T, Nahlik L, Maleckar S, Kasza K, Ang-Lee M, Moss J. Brief communication: American ginseng reduces warfarin's effect in healthy patients: a randomized, controlled trial. Ann Intern Med 2004;141:23-7. https://doi.org/10.7326/0003-4819-141-1-200407060-00011
  8. Shin BK, Kwon SW, Park JH. Chemical diversity of ginseng saponins from Panax ginseng. J Ginseng Res 2015;39:287-98. https://doi.org/10.1016/j.jgr.2014.12.005
  9. Hasani-Ranjbar S, Nayebi N, Larijani B, Abdollahi M. A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. World J Gastroenterol 2009;15:3073-85. https://doi.org/10.3748/wjg.15.3073
  10. Lu JM, Yao Q, Chen C. Ginseng compounds: an update on their molecular mechanisms and medical applications. Curr Vasc Pharmacol 2009;7:293-302. https://doi.org/10.2174/157016109788340767
  11. Baeg IH, So SH. The world ginseng market and the ginseng (Korea). J Ginseng Res 2013;37:1-7. https://doi.org/10.5142/jgr.2013.37.1
  12. Bae JK, Kim YJ, Chae HS, Kim DY, Choi HS, Chin YW, Choi YH. Korean red ginseng extract enhances paclitaxel distribution to mammary tumors and its oral bioavailability by P-glycoprotein inhibition. Xenobiotica 2016;17:1-10.
  13. Lee S, Park JM, Jeong M, Han YM, Go EJ, Ko WJ, Cho JY, Kwon CI, Hahm KB. Korean red ginseng ameliorated experimental pancreatitis through the inhibition of hydrogen sulfide in mice. Pancreatology 2016;16:326-36. https://doi.org/10.1016/j.pan.2016.02.012
  14. Wang CZ, Anderson S, Du W, He TC, Yuan CS. Red ginseng and cancer treatment. Chin J Nat Med 2016;14:7-16.
  15. Jung SY, Kim C, Kim WS, Lee SG, Lee JH, Shim BS, Kim SH, Ahn KS. Korean red ginseng extract enhances the anticancer effects of Imatinib mesylate through abrogation p38 and STAT5 activation in KBM-5 cells. Phytother Res 2015;29: 1062-72. https://doi.org/10.1002/ptr.5347
  16. Kim H, Hong MK, Choi H, Moon HS, Lee HJ. Chemopreventive effects of Korean red ginseng extract on rat hepatocarcinogenesis. J Cancer 2015;6:1-8. https://doi.org/10.7150/jca.10353
  17. Jin X, Che DB, Zhang ZH, Yan HM, Jia ZY, Jia XB. Ginseng consumption and risk of cancer: a meta-analysis. J Ginseng Res 2016;40:269-77. https://doi.org/10.1016/j.jgr.2015.08.007
  18. Yun TK. Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds. Mutat Res 2003;523-524:63-74. https://doi.org/10.1016/S0027-5107(02)00322-6
  19. Sun S, Qi LW, Du GJ, Mehendale SR, Wang CZ, Yuan CS. Red notoginseng: higher ginsenoside content and stronger anticancer potential than Asian and American ginseng. Food Chem 2011;125:1299-305. https://doi.org/10.1016/j.foodchem.2010.10.049
  20. Kim JY, Lee YG, Kim MY, Byeon SE, Rhee MH, Park J, Katz DR, Chain BM, Cho JY. Src-mediated regulation of inflammatory responses by actin polymerization. Biochem Pharmacol 2010;79:431-43. https://doi.org/10.1016/j.bcp.2009.09.016
  21. Kim SN, Lee HJ, Jeon MS, Yi T, Song SU. Galectin-9 is involved in immunosuppression mediated by human bone marrow-derived clonal mesenchymal stem cells. Immune Netw 2015;15:241-51. https://doi.org/10.4110/in.2015.15.5.241
  22. Yi YS, Baek KS, Cho JY. L1 cell adhesion molecule induces melanoma cell motility by activation of mitogen-activated protein kinase pathways. Pharmazie 2014;69:461-7.
  23. Won KJ, Park SW, Lee S, Kong IK, Chae JI, Kim B, Lee EJ, Kim DK. A new triggering receptor expressed on myeloid cells (TREM) family member, TLT-6, is involved in activation and proliferation of macrophages. Immune Netw 2015;15:232-40. https://doi.org/10.4110/in.2015.15.5.232
  24. Jeong D, Yi YS, Sung GH, Yang WS, Park JG, Yoon K, Yoon DH, Song C, Lee Y, Rhee MH, et al. Anti-inflammatory activities and mechanisms of Artemisia asiatica ethanol extract. J Ethnopharmacol 2014;152:487-96. https://doi.org/10.1016/j.jep.2014.01.030
  25. Shalini S, Dorstyn L, Dawar S, Kumar S. Old, new and emerging functions of caspases. Cell Death Differ 2015;22:526-39. https://doi.org/10.1038/cdd.2014.216
  26. Goodsell DS. The molecular perspective: caspases. Oncologist 2000;5:435-6. https://doi.org/10.1634/theoncologist.5-5-435
  27. McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol 2013;5:a008656.
  28. Shi Y. Caspase activation: revisiting the induced proximity model. Cell 2004;117:855-8. https://doi.org/10.1016/j.cell.2004.06.007
  29. Sollberger G, Strittmatter GE, Garstkiewicz M, Sand J, Beer HD. Caspase-1: the inflammasome and beyond. Innate Immun 2014;20:115-25. https://doi.org/10.1177/1753425913484374
  30. Riedl SJ, Shi Y. Molecular mechanisms of caspase regulation during apoptosis. Nat Rev Mol Cell Biol 2004;5:897-907.

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