Journal of Ginseng Research

  • 제39권3호
  • /
  • Pages.230-237
  • /
  • 2015
  • /
  • 1226-8453(pISSN)
  • /
  • 2093-4947(eISSN)
고려인삼학회 (The Korean Society of Ginseng)
권호 표지
DOI QR코드

DOI QR Code

American ginseng significantly reduced the progression of high-fat-diet-enhanced colon carcinogenesis in ApcMin/+ mice

  • Yu, Chunhao (School of Life Science and Chemical Engineering, Huaiyin Institute of Technology) ;
  • Wen, Xiao-Dong (Tang Center for Herbal Medicine Research, University of Chicago) ;
  • Zhang, Zhiyu (Tang Center for Herbal Medicine Research, University of Chicago) ;
  • Zhang, Chun-Feng (Tang Center for Herbal Medicine Research, University of Chicago) ;
  • Wu, Xiaohui (Tang Center for Herbal Medicine Research, University of Chicago) ;
  • He, Xin (Tang Center for Herbal Medicine Research, University of Chicago) ;
  • Liao, Yang (Tang Center for Herbal Medicine Research, University of Chicago) ;
  • Wu, Ningning (Tang Center for Herbal Medicine Research, University of Chicago) ;
  • Wang, Chong-Zhi (Tang Center for Herbal Medicine Research, University of Chicago) ;
  • Du, Wei (Tang Center for Herbal Medicine Research, University of Chicago) ;
  • He, Tong-Chuan (Tang Center for Herbal Medicine Research, University of Chicago) ;
  • Yuan, Chun-Su (Tang Center for Herbal Medicine Research, University of Chicago)
  • 투고 : 2014.08.13
  • 심사 : 2014.12.24
  • 발행 : 2015.07.15
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. Methods: A genetically engineered $Apc^{Min/+}$ mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. Results: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-$1{\alpha}$ (IL-$1{\alpha}$), IL-$1{\beta}$, IL-6, tumor necrosis factor-${\alpha}$, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Conclusion: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

키워드

참고문헌

  1. National Cancer Institute. Colon and rectal cancer. [Internet]. Bethesda (MD): NCI; 2014. [cited 2014 Jun 2] Available from:, http://www.cancer.gov/ cancertopics/types/colon-and-rectal.
  2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64: 104-17. https://doi.org/10.3322/caac.21220
  3. National Cancer Institute. SEER stat fact sheets: colon and rectum. [Internet]. Bethesda (MD): NCI; 2014. [cited 2014 Jun 2] Available from:, http://seer. cancer.gov/statfacts/html/colorect.html#risk.
  4. Yun TK, Choi SY. Preventive effect of ginseng intake against various human cancers: a case-control study on 1987 pairs. Cancer Epidemiol Biomarkers Prev 1995;4:401-8.
  5. Yun TK. Panax ginseng―a non-organ-specific cancer preventive? Lancet Oncol 2001;2:49-55. https://doi.org/10.1016/S1470-2045(00)00196-0
  6. Gu C, Qiao J, Zhu M, Du J, Shang W, Yin W, Wang W, Han M, Lu W. Preliminary evaluation of the interactions of Panax ginseng and Salvia miltiorrhiza Bunge with 5-fluorouracil on pharmacokinetics in rats and pharmacodynamics in human cells. Am J Chin Med 2013;41:443-58. https://doi.org/10.1142/S0192415X13500328
  7. Park EY, Kim MH, Kim EH, Lee EK, Park IS, Yang DC, Jun HS. Efficacy comparison of Korean ginseng and American ginseng on body temperature and metabolic parameters. Am J Chin Med 2014;42:173-87. https://doi.org/10.1142/S0192415X14500128
  8. McCarthy N. Tumorigenesis: all together now. Nat Rev Cancer 2013;13: 148-9. https://doi.org/10.1038/nrc3469
  9. Lewis B, Lin J, Wu X, Xie H, Shen B, Lai K, Manilich E, Liu X. Crohn's disease-like reaction predicts favorable prognosis in colitis-associated colorectal cancer. Inflamm Bowel Dis 2013;19:2190-8. https://doi.org/10.1097/MIB.0b013e31829e13e1
  10. Foersch S, Waldner MJ, Neurath MF. Colitis and colorectal cancer. Dig Dis 2012;30:469-76. https://doi.org/10.1159/000341692
  11. Xiaoguang C, Hongyan L, Xiaohong L, Zhaodi F, Yan L, Lihua T, Rui H. Cancer chemopreventive and therapeutic activities of red ginseng. J Ethnopharmacol 1998;60:71-8. https://doi.org/10.1016/S0378-8741(97)00133-5
  12. Shibata S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci 2001;16:S28-37. https://doi.org/10.3346/jkms.2001.16.S.S28
  13. Qi LW, Wang CZ, Yuan CS. American ginseng: potential structure-function relationship in cancer chemoprevention. Biochem Pharmacol 2010;80:947-54. https://doi.org/10.1016/j.bcp.2010.06.023
  14. Poudyal D, Le PM, Davis T, Hofseth AB, Chumanevich A, Chumanevich AA, Wargovich MJ, Nagarkatti M, Nagarkatti PS, Windust A, et al. A hexane fraction of American ginseng suppresses mouse colitis and associated colon cancer: anti-inflammatory and proapoptotic mechanisms. Cancer Prev Res (Phila) 2012;5:685-96. https://doi.org/10.1158/1940-6207.CAPR-11-0421
  15. Hofseth LJ, Wargovich MJ. Inflammation, cancer, and targets of ginseng. J Nutr 2007;137:S183-5. https://doi.org/10.1093/jn/137.1.183S
  16. Zhu J, Jiang Y, Wu L, Lu T, Xu G, Liu X. Suppression of local inflammation contributes to the neuroprotective effect of ginsenoside Rb1 in rats with cerebral ischemia. Neuroscience 2012;202:342-51. https://doi.org/10.1016/j.neuroscience.2011.11.070
  17. Jin Y, Hofseth AB, Cui X, Windust AJ, Poudyal D, Chumanevich AA, Matesic LE, Singh NP, Nagarkatti M, Nagarkatti PS, et al. American ginseng suppresses colitis through p53-mediated apoptosis of inflammatory cells. Cancer Prev Res (Phila) 2010;3:339-47. https://doi.org/10.1158/1940-6207.CAPR-09-0116
  18. Benbrook DM, Guruswamy S, Wang Y, Sun Z, Mohammed A, Zhang Y, Li Q, Rao CV. Chemoprevention of colon and small intestinal tumorigenesis in $APC^{min/+}$ mice by SHetA2 (NSC721689) without toxicity. Cancer Prev Res (Phila) 2013;6:908-16. https://doi.org/10.1158/1940-6207.CAPR-13-0171
  19. Derry MM, Raina K, Balaiya V, Jain AK, Shrotriya S, Huber KM, Serkova NJ, Agarwal R, Agarwal C. Grape seed extract efficacy against azoxymethaneinduced colon tumorigenesis in A/J mice: interlinking miRNA with cytokine signaling and inflammation. Cancer Prev Res (Phila) 2013;6:625-33. https://doi.org/10.1158/1940-6207.CAPR-13-0053
  20. Khan R, Khan AQ, Lateef A, Rehman MU, Tahir M, Ali F, Hamiza OO, Sultana S. Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats. PLoS One 2013;8:e56020. https://doi.org/10.1371/journal.pone.0056020
  21. Qi LW, Wang CZ, Yuan CS. Ginsenosides from American ginseng: chemical and pharmacological diversity. Phytochemistry 2011;72:689-99. https://doi.org/10.1016/j.phytochem.2011.02.012
  22. 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 InternMed 2004;141:23-7. https://doi.org/10.7326/0003-4819-141-1-200407060-00011
  23. Christensen LP. Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res 2009;55:1-99.
  24. Qi LW, Wang CZ, Yuan CS. Isolation and analysis of ginseng: advances and challenges. Nat Prod Rep 2011;28:467-95. https://doi.org/10.1039/c0np00057d
  25. Baek SH, Bae ON, Park JH. Recent methodology in ginseng analysis. J Ginseng Res 2012;36:119-34. https://doi.org/10.5142/jgr.2012.36.2.119
  26. Wang CZ, Du GJ, Zhang Z, Wen XD, Calway T, Zhen Z, Musch MW, Bissonnette M, Chang EB, Yuan CS. Ginsenoside compound K, not Rb1, possesses potential chemopreventive activities in human colorectal cancer. Int J Oncol 2012;40:1970-6.
  27. Jin HR, Zhao J, Zhang Z, Liao Y, Wang CZ, Huang WH, Li SP, He TC, Yuan CS, Du W. The antitumor natural compound falcarindiol promotes cancer cell death by inducing endoplasmic reticulum stress. Cell Death Dis 2012;3:e376. https://doi.org/10.1038/cddis.2012.122
  28. Fichera A, Guo Y, Romero L, Michelassi F, Arenas RB. Quantitation of in vivo gene delivery by restriction enzyme PCR generated polymorphism. J Surg Res 1997;69:188-92. https://doi.org/10.1006/jsre.1997.5073
  29. Paturi G, Mandimika T, Butts CA, Zhu S, Roy NC, McNabb WC, Ansell J. Influence of dietary blueberry and broccoli on cecal microbiota activity and colon morphology in $mdr1a^{-/-}$ mice, a model of inflammatory bowel diseases. Nutrition 2012;28:324-30. https://doi.org/10.1016/j.nut.2011.07.018
  30. Mohammed A, Janakiram NB, Li Q, Choi CI, Zhang Y, Steele VE, Rao CV. Chemoprevention of colon and small intestinal tumorigenesis in $APC^{min/+}$ mice by licofelone, a novel dual 5-LOX/COX inhibitor: potential implications for human colon cancer prevention. Cancer Prev Res (Phila) 2011;4:2015-26. https://doi.org/10.1158/1940-6207.CAPR-11-0233
  31. 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
  32. Qi LW, Wang HY, Zhang H, Wang CZ, Li P, Yuan CS. Diagnostic ion filtering to characterize ginseng saponins by rapid liquid chromatography with time-offlight mass spectrometry. J Chromatogr A 2012;1230:93-9. https://doi.org/10.1016/j.chroma.2012.01.079
  33. Wan JY, Liu P, Wang HY, Qi LW, Wang CZ, Li P, Yuan CS. Biotransformation and metabolic profile of American ginseng saponins with human intestinal microflora by liquid chromatography quadrupole time-of-flight mass spectrometry. J Chromatogr A 2013;1286:83-92. https://doi.org/10.1016/j.chroma.2013.02.053
  34. Wang CZ, Aung HH, Ni M, Wu JA, Tong R, Wicks S, He TC, Yuan CS. Red American ginseng: ginsenoside constituents and antiproliferative activities of heat-processed Panax quinquefolius roots. Planta Med 2007;73:669-74. https://doi.org/10.1055/s-2007-981524
  35. Wang CZ, Ni M, Sun S, Li XL, He H, Mehendale SR, Yuan CS. Detection of adulteration of notoginseng root extract with other panax species by quantitative HPLC coupled with PCA. J Agric Food Chem 2009;57:2363-7. https://doi.org/10.1021/jf803320d
  36. Dougherty U, Mustafi R, Wang Y, Musch MW, Wang CZ, Konda VJ, Kulkarni A, Hart J, Dawson G, Kim KE, et al. American ginseng suppresses Western dietpromoted tumorigenesis in model of inflammation-associated colon cancer: role of EGFR. BMC Complement Altern Med 2011;11:111-21. https://doi.org/10.1186/1472-6882-11-111
  37. Madka V, Rao CV. Anti-inflammatory phytochemicals for chemoprevention of colon cancer. Curr Cancer Drug Targets 2013;13:542-57. https://doi.org/10.2174/15680096113139990036
  38. Garcia Rodriguez LA, Cea-Soriano L, Tacconelli S, Patrignani P. Coxibs: pharmacology, toxicity and efficacy in cancer clinical trials. Recent Results Cancer Res 2013;191:67-93. https://doi.org/10.1007/978-3-642-30331-9_4
  39. Zhou Y, Boudreau DM, Freedman AN. Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population. Pharmacoepidemiol Drug Saf 2014;23:43-50. https://doi.org/10.1002/pds.3463
  40. Chen S, Qu X, Wan P, Li QW, Wang Z, Guo F, Bai L, Hu Z, Tan W, Li J. Norcantharidin inhibits pre-replicative complexes assembly of HepG2 cells. Am J Chin Med 2013;41:665-82. https://doi.org/10.1142/S0192415X13500468
  41. Liu S, Wang XJ, Liu Y, Cui YF. PI3K/AKT/mTOR signaling is involved in (-)-epigallocatechin-3-gallate-induced apoptosis of human pancreatic carcinoma cells. Am J Chin Med 2013;41:629-42. https://doi.org/10.1142/S0192415X13500444
  42. Wang CY, Bai XY, Wang CH. Traditional Chinese medicine: a treasured natural resource of anticancer drug research and development. Am J Chin Med 2014;42:543-59. https://doi.org/10.1142/S0192415X14500359
  43. Park EH, Kim YJ, Yamabe N, Park SH, Kim HK, Jang HJ, Kim JH, Cheon GJ, Ham J, Kang KS. Stereospecific anticancer effects of ginsenoside Rg3 epimers isolated from heat-processed American ginseng on human gastric cancer cell. J Ginseng Res 2014;38:22-7. https://doi.org/10.1016/j.jgr.2013.11.007
  44. De Robertis M, Massi E, Poeta ML, Carotti S, Morini S, Cecchetelli L, Signori E, Fazio VM. The AOM/DSS murine model for the study of colon carcinogenesis: from pathways to diagnosis and therapy studies. J Carcinog 2011;10:9. https://doi.org/10.4103/1477-3163.78279
  45. Wen XD, Wang CZ, Yu C, Zhang Z, Calway T, Wang Y, Li P, Yuan CS. Salvia miltiorrhiza (dan shen) significantly ameliorates colon inflammation in dextran sulfate sodium induced colitis. Am J Chin Med 2013;41:1097-108. https://doi.org/10.1142/S0192415X13500742
  46. Day SD, Enos RT, McClellan JL, Steiner JL, Velázquez KT, Murphy EA. Linking inflammation to tumorigenesis in a mouse model of high-fat-diet-enhanced colon cancer. Cytokine 2013;64:454-62. https://doi.org/10.1016/j.cyto.2013.04.031
  47. Jacoby RF, Seibert K, Cole CE, Kelloff G, Lubet RA. The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res 2000;60:5040-4.
  48. Yuan CS, Wang CZ, Wicks SM, Qi LW. Chemical and pharmacological studies of saponins with a focus on American ginseng. J Ginseng Res 2010;34:160-7. https://doi.org/10.5142/jgr.2010.34.3.160
  49. Tawab MA, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M. Degradation of ginsenosides in humans after oral administration. Drug Metab Dispos 2003;31:1065-71. https://doi.org/10.1124/dmd.31.8.1065
  50. Hasegawa H. Proof of the mysterious efficacy of ginseng: basic and clinical trials: metabolic activation of ginsenoside: deglycosylation by intestinal bacteria and esterification with fatty acid. J Pharmacol Sci 2004;95:153-7. https://doi.org/10.1254/jphs.FMJ04001X4
  51. Oh GS, Pae HO, Choi BM, Seo EA, Kim DH, Shin MK, Kim JD, Kim JB, Chung HT. 20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide. Cancer Lett 2004;205:23-9. https://doi.org/10.1016/j.canlet.2003.09.037
  52. Punja ZK. American ginseng: research developments, opportunities, and challenges. J Ginseng Res 2011;35:368-74. https://doi.org/10.5142/jgr.2011.35.3.368

피인용 문헌

  1. Metabonomic Profiling Reveals Cancer Chemopreventive Effects of American Ginseng on Colon Carcinogenesis in ApcMin/+ Mice vol.14, pp.8, 2015, https://doi.org/10.1021/acs.jproteome.5b00388
  2. A Nucleotide Signature for the Identification of American Ginseng and Its Products vol.7, pp.None, 2015, https://doi.org/10.3389/fpls.2016.00319
  3. New frontiers in the treatment of colorectal cancer: Autophagy and the unfolded protein response as promising targets vol.13, pp.5, 2017, https://doi.org/10.1080/15548627.2017.1290751
  4. Daikenchuto (TU‐100) Suppresses Tumor Development in the Azoxymethane and APCmin/+ Mouse Models of Experimental Colon Cancer vol.31, pp.1, 2015, https://doi.org/10.1002/ptr.5735
  5. Significant difference in active metabolite levels of ginseng in humans consuming Asian or Western diet: The link with enteric microbiota vol.31, pp.4, 2017, https://doi.org/10.1002/bmc.3851
  6. Role of intestinal microbiome in American ginseng-mediated colon cancer protection in high fat diet-fed AOM/DSS mice vol.20, pp.3, 2018, https://doi.org/10.1007/s12094-017-1717-z
  7. Comparison of Serum Metabolite Changes of Radiated Mice Administered with Panax quinquefolium from Different Cultivation Regions Using UPLC-Q/TOF-MS Based Metabolomic Approach vol.23, pp.5, 2018, https://doi.org/10.3390/molecules23051014