DOI QR코드

DOI QR Code

Shipyeukmiyeugi-eum Extracts Suppressed Tumor Growth through Immunomodulatory Effects on MCF-7

십육미유기음(十六味流氣飮)의 면역활성(免疫活性)에 의한 유방암(乳房癌) 세포 성장억제효과(成長抑制效果)

  • Jung, Yeon-Chul (Dept. of Oriental Obstetrics & Gynecology, College of Oriental Medicine, Daeguhaany University) ;
  • Park, Young-Sun (Dept. of Oriental Obstetrics & Gynecology, College of Oriental Medicine, Daeguhaany University) ;
  • Kim, Dong-Chul (Dept. of Oriental Obstetrics & Gynecology, College of Oriental Medicine, Daeguhaany University)
  • 정연철 (대구한의대학교 한의과대학 부인과교실) ;
  • 박영선 (대구한의대학교 한의과대학 부인과교실) ;
  • 김동철 (대구한의대학교 한의과대학 부인과교실)
  • Received : 2012.07.25
  • Accepted : 2012.08.16
  • Published : 2012.08.31

Abstract

Objectives: The object of this study was to observe antitumor, anticachexia and immunomodulatory effects of Shipyeukmiyeugi-eum(SYM) on human breast cancer cell, MCF-7, xenograft Balb/c nu-nu nude mice. Methods: Three different dosages of SYM-125, 250 and 500 mg/kg were orally administered once a day for 28 days from 11 days after tumor cell inoculation, and the changes on the body weights, tumor volume and weights, weights of spleen and popliteal lymph node and epididymal fat, serum IL-6 and IFN-${\gamma}$ levels, NK cell and peritoneal macrophage activities, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents were observed. In addition, histopathological observations of apoptotic cell, spleen, popliteal lymph node and cervical brown adipose were also detected. The results were compared with a potent cytotoxic estrogen receptor antagonist, Tamoxifen 20 mg/kg treated mice. Results: Tumor volumes and weights were decreased without cytotoxic effects on the both MCF-7 and MCF-10A cells as results of all three different dosages of SYM treatment. And weights of body, spleen, popliteal lymph node, epididymal fat, serum IFN-${\gamma}$, NK cell, peritoneal macrophage activities, splenic TNF-${\alpha}$, IL-$1{\beta}$ and IL-10 contents were increased with decrease of serum IL-6. At histopathological observations, apoptotic tumor cells, spleen, popliteal lymph node and cervical brown adipose tissue were increased. That means tumor-related immunosuppress and cachexia were markedly inhibited by SYM treatment as compared with tumor-bearing mice. On the other hand, Tamoxifen showed marked cytotoxic effects against MCF-7 and MCF-10A, decreases of tumor volume and weights, and increases of apoptotic tumor cells and related decreases of tumor cell volumes, but tamoxifen markedly deteriorated the tumor-related immune-suppress and cachexia. Conclusions: The results obtained in this study suggest that SYM showed favorable anticancer effects and anticachexic effects on the MCF-7 cell xenograft through immunomodulatory effects. SYM did not induce any cytotoxic effects against both normal and cancer cells.

Keywords

References

  1. 보건복지가족부. 국가암등록사업 연례보고서. 2009. available from: URL: http://www.mw.go.kr/front/index.jsp.
  2. Oka M et al. Relationship between serum levels of Il-6, various disease parameters and malnutrition in patients with esophageal squamous cell carcinoma. Cancer Res. 1996;56(12):2776-80.
  3. Ha ES et al. Anti-metastatic activity of glycoprotein fractionated from Acanthpanax senticosus, involvement of NK-cell and macrophage activation. Arch Pharm Res. 2004;27(2):217-24. https://doi.org/10.1007/BF02980109
  4. Yu GM, Hwang IG. In vitro effect of Yuza(Citrus junos SIEB ex TANAKA) extracts on proliferation of human prostate cancer cells and antioxidant activity. Korean J Food Sci Technol. 2004;36:339-44.
  5. 陳夢雷 等. 古今圖書集成 醫部全錄. 9冊. 北京:人民衛生出版社. 1983:54, 135.
  6. Detre S et al. Comparison of the selective estrogen receptor modulator arzoxifene(LY353381) with tamoxifen on tumor growth and biomarker expression in an MCF-7 human breast cancer xenograft model. Cancer Res. 2003;63(19):6516-22.
  7. Nishimura G et al. An antioxidant, probucol, induces anti-angiogenesis and apoptosis in athymic nude mouse xenografted human head and neck squamous carcinoma cells. Jpn J Cancer Res. 1999;90(11):1224-30. https://doi.org/10.1111/j.1349-7006.1999.tb00700.x
  8. Iizuka N et al. Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6. Cancer Lett. 2000;158(1):35-41. https://doi.org/10.1016/S0304-3835(00)00496-1
  9. Zarling JM et al. Augmentation of natural killer cell activity by polyinosinic acid-polycytidylic acid and its nontoxic mismatched analogues. J Immunol. 1980;124(4):1852-7.
  10. Clark BD et al. Detection of interleukin 1 alpha and 1 beta in rabbit tissues during endotoxemia using sensitive radio immunoassays. J Appl Physiol. 1991;71(6):2412-8.
  11. Hotchkiss RS et al. Calcium antagonists decrease plasma and tissue concentrations of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-1 alpha in a mouse model of endotoxin. Shock. 1995;3(5):337-42.
  12. Liu L et al. Clinical and experimental study on regional administration of phosphorus 32 glass microspheres in treating hepatic carcinoma. World J Gastroenterol. 1999;5(6):492-505. https://doi.org/10.3748/wjg.v5.i6.492
  13. 국가 암정보센터. available from: URL: http://www.cancer.go.kr/
  14. 翁家武, 陳培丰. 癌症惡病質的中醫藥 治療硏究進展. 浙江:中西醫結合雜誌. 2009;19(2):271-80.
  15. 許浚. 東醫寶鑑 外形偏. 서울:대성문화사. 1992:407, 414.
  16. 김정진 등. 유방종괴에 관한 문헌적 고찰. 대한한방부인과학회지. 1998; 11(2):29-43.
  17. Makino T et al. Suppressive effects of Perilla frutescens on IgA nephropathy in HIGA mice. Nephrol Dial Transplant. 2003;18(3):484-90. https://doi.org/10.1093/ndt/18.3.484
  18. Oh HA et al. Effect of Perilla frutescens var. acuta Kudo and rosmarinic acid on allergic inflammatory reactions. Exp Biol Med(Maywood). 2011;236(1): 99-106. https://doi.org/10.1258/ebm.2010.010252
  19. Jang HI, Shin HM. Wild Panax ginseng (Panax ginseng C.A. Meyer) protects against methotrexate-induced cell regression by enhancing the immune response in RAW 264.7 macrophages. Am J Chin Med. 2010;38(5):949-60. https://doi.org/10.1142/S0192415X10008378
  20. Ni W et al. Antitumor activities and immune modulatory effects of ginseng neutral polysaccharides in combination with 5-fluorouracil. J Med Food. 2010;13(2):270-7. https://doi.org/10.1089/jmf.2009.1119
  21. Clement-Kruzel S et al. Immune modulation of macrophage pro-inflammatory response by goldenseal and Astragalus extracts. J Med Food. 2008;11(3): 493-8. https://doi.org/10.1089/jmf.2008.0044
  22. Han SB et al. Characteristic immune stimulation by angelan isolated from Angelica gigas Nakai. Immunopharmacology. 1998;40(1):39-48. https://doi.org/10.1016/S0162-3109(98)00026-5
  23. 임강현 등. 백지의 사람비만세포 사이토카인 및 케모카인 발현 양상. 대한본초학회지. 2007;22:81-7.
  24. Luo Y et al. Total alkaloids from Radix Linderae prevent the production of inflammatory mediators in lipopoly saccharide-stimulated RAW 264.7 cells by suppressing NF-kappa B and MAPKs activation. Cytokine. 2009; 46(1):104-10. https://doi.org/10.1016/j.cyto.2008.12.017
  25. Jeong JB et al. Antioxidant activity in essential oils of Cnidium officinale makino and Ligusticum chuanxiong Hort and their inhibitory effects on DNA damage and apoptosis induced by ultraviolet B in mammalian cell. Cancer Epidemiol. 2009;33(1):41-6. https://doi.org/10.1016/j.canep.2009.04.010
  26. Jeong JB et al. Protective effect of the extracts from Cnidium officinale against oxidative damage induced by hydrogen peroxide via antioxidant effect. Food Chem Toxicol. 2009;47(3): 525-9. https://doi.org/10.1016/j.fct.2008.11.039
  27. Kim NY, Ryu JH. Butanolides from Machilus thunbergii and their inhibitory activity on nitricoxide synthesis in activated macrophages. Phytother Res. 2003;17(4):372-5. https://doi.org/10.1002/ptr.1160
  28. Tai J, Cheung S. Anti-proliferative and antioxidant activities of Saposhnikovia divaricata. Oncol Rep. 2007;18(1): 227-34.
  29. Pithayanukul P et al. Hepa toprotective potential of extracts from seeds of Areca catechu and nutgalls of Quercus infectoria. Molecules. 2009;14(12):4987-5000. https://doi.org/10.3390/molecules14124987
  30. 정연희, 채병윤. 십육미유기음(十六味流氣飮) 및 그 가미방이 갑상선 기능에 미치는 영향. 대한한의학회지. 1988;9:98-108.
  31. 李枝映 등. 十六味流氣飮煎湯液이 實驗動物에 미치는 影響. 원광한의학. 1993;3:149-65.
  32. 沈相姬. 十六味流氣飮의 항암 및 항암제 부작용에 미치는 영향. 2003. 동신대학교 대학원.
  33. 洪淳昇. 洪家定診秘傳. 서울:醫藥社. 1974:67-9, 75.
  34. 朴南錯. 韓方治療大全. 서울:南山堂. 1979:125, 349.
  35. 朴炳昆. 漢方臨床 40年. 서울:大成文化社. 1984:334-8.
  36. 李基淳. 漢方內科學. 서울:壽文社. 1982: 300, 372.
  37. Yaacob NS et al. Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthescrispus on human breast and prostate cancer cells in vitro. BMC Complement Altern Med. 2010;5(10):42.
  38. 김정숙 등. 유용에 활용되는 가감유기음에 대한 실험적연구. 대한한방부인과학회지. 1995;8(1):115-30.
  39. Kurebayashi.J et al. Medroxyproges terone acetate inhibits interleukin 6 secretion from KPL-4 human breast cancer cells both in vitro and in vivo: a possible mechanism of the anticachectic effect. Br J Cancer. 1999;79(3-4):631-6. https://doi.org/10.1038/sj.bjc.6690099
  40. Isaacs A. Lymphokines and Cytokines. In:Immunology an introduction (Tizard IR editor). 4th edition. Saunders: Philadelphia, 1995:155-69.
  41. 서울대학교의과대학 편. 종양학. 서울:서울대학교출판부. 1998:229.
  42. Ripoll V.M. et al. Microphthlmia transcription factor regulates the expression of the novel osteoclast factor GPNMB. Gene. 2008;413(1-2): 32-41. https://doi.org/10.1016/j.gene.2008.01.014
  43. Unanue ER. The Mononuclear-Phagocytic Sytem. In:Immunology an introduction (Tizard IR editor). 4th edition. Saunders:Philadelphia. 1995:61-74.
  44. Joffroy CM et al. Antiestrogens induce transforming growth factor beta-mediated immune suppression in breast cancer. Cancer Res. 2010; 70(4):1314-22. https://doi.org/10.1158/0008-5472.CAN-09-3292