동의생리병리학회지 (Journal of Physiology & Pathology in Korean Medicine)

  • 제28권2호
  • /
  • Pages.162-168
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  • 2014
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  • 1738-7698(pISSN)
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  • 2288-2529(eISSN)
대한동의생리학회·한의병리학회 ( The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine)
권호 표지

오미자의 유방암 세포사멸과 TRPM7 관련성에 관한 연구

Effects of Schisandra Chinensis on Human Breast Cancer Cells

  • 김정남 (부산대학교 한의학전문대학원 양생기능의학부) ;
  • 채한 (부산대학교 한의학전문대학원 양생기능의학부) ;
  • 권영규 (부산대학교 한의학전문대학원 양생기능의학부) ;
  • 김병주 (부산대학교 한의학전문대학원 양생기능의학부)
  • Kim, Jung Nam (Division of Longevity and Biofunctional Medicine, College of Korean Medicine, Pusan National University) ;
  • Chae, Han (Division of Longevity and Biofunctional Medicine, College of Korean Medicine, Pusan National University) ;
  • Kwon, Young Kyu (Division of Longevity and Biofunctional Medicine, College of Korean Medicine, Pusan National University) ;
  • Kim, Byung Joo (Division of Longevity and Biofunctional Medicine, College of Korean Medicine, Pusan National University)
  • 투고 : 2014.02.14
  • 심사 : 2014.03.10
  • 발행 : 2014.04.25
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초록

Fruits of Schisandra chinensis (SC) Baill are considered a traditional herbal medicine for the treatment and alleviation of various diseases. The purpose of this study was to investigate the anti-cancer effects of SC extract in human breast adenocarcinoma cells (MCF-7). We used human breast adenocarcinoma cell line, MCF-7 cells. We examined cell death by MTT assay and caspase 3 and 9 assay with SC extract. To examine the inhibitory effects of SC extract, cell cycle (sub G1) analysis and mitochondrial membrane depolarization was done the MCF-7 cells after one day with SC extract. In addition, to investigate the transient receptor potential melastatin 7 (TRPM7) currents, we used the whole cell patch clamp techniques. Furthermore, TRPM7 channels were overexpressed in human embryonic kidney (HEK) 293 cells to identify the role of TRPM7 channels in MCF-7 cell growth and survival. SC extract inhibited the growth of MCF-7 cells in a dose-dependent fashion. Also we showed that SC extract induced apoptosis in MCF-7 cells by MTT assay, caspase 3 and 9 assay, sub-G1 analysis and mitochondrial membrane depolarization. SC extract inhibited the TRPM7 currents in MCF-7 cells and in TRPM7 overexpressed HEK 293 cells. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated SC extract-induced cell death. Our findings provide insight into unraveling the effects of SC extract in human breast adenocarcinoma cells and developing therapeutic agents against breast cancer.

키워드

참고문헌

  1. 보건복지부 중앙암등록본부. www.ncc.re.kr
  2. www.cancer.go.kr
  3. Scaffidi, C., Fulda, S., Srinivasan, A., Friesen, C., Li, F., Tomaselli, K.J., Debatin, K.M., Krammer, P.H., Peter, M.E. Two CD95 (APO-1/Fas) signaling pathways. EMBO J 17: 1675-1687, 1998. https://doi.org/10.1093/emboj/17.6.1675
  4. Lawen, A. Apoptosis - an introduction. Bioessays 25: 888-896, 2003. https://doi.org/10.1002/bies.10329
  5. Jin, Z., El-Deiry, W.S. Overview of cell death signaling pathways. Cancer Biol Ther 4: 139-163, 2005.
  6. Kroemer, G., Reed, J.C. Mitochondrial control of cell death. Nat Med 6: 513-519, 2000. https://doi.org/10.1038/74994
  7. Liu, X., Kim, C.N., Yang, J., Jemmerson, R., Wang, X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86: 147-157, 1996. https://doi.org/10.1016/S0092-8674(00)80085-9
  8. 한송이, 김정아, 송호준, 채한, 권영규, 김병주. 홍화가 인체 대 장암세포에 미치는 효과. 동의병리생리학회지 17(2):129-134, 2011.
  9. 김정아, 한송이, 송호준, 채한, 권영규, 김병주. 홍화가 인체 위암세포에 미치는 효과. 동의병리생리학회지 25(3):466-470, 2011.
  10. Kim, B.J., Nah, S.Y., Jeon, J.H., So, I., Kim, S.J. Transient Receptor Potential Melastatin 7 Channels are Involved in Ginsenoside Rg3-Induced Apoptosis in Gastric Cancer Cells. Basic & Clinical Pharmacology & Toxicology 109: 233-239, 2011. https://doi.org/10.1111/j.1742-7843.2011.00706.x
  11. 이희정, 김민철, 임보라, 배고은, 김형우, 권영규, 김병주. 고삼의 인체 유방암세포에 미치는 효과. 한국한의학연구원논문집 18(1):75-84, 2012.
  12. 임보라, 이희정, 김민철, 김형우, 김병주. 인체 위암세포에서 고삼의 세포사멸효과. 한국한의학연구원논문집 18(1):85-92, 2012.
  13. Sung, K.C. A study on the pharmaceutical & chemical characteristics and analysis of natural omija extract. J Korean Oil Chemists' Soc 28: 290-298, 2011.
  14. Cho, Y.J., Ju, I.S., Kim, B.C., Lee, W.S., Kim, M.J., Lee, B.G., An, B.J., Kim, J.H., Kwon, O.J. Biological activity of Omija (Schisandra chinensis Baillon) extracts. J Korean Soc Appl Biol Chem 50: 198-203, 2007.
  15. Kim, H.K., Na, G.M., Ye, S.H., Han, H.S. Extraction characteristics and antioxidative activity of Schisandra chinensis extracts. Korean J Food Culture 19: 484-490, 2004.
  16. Lee, M.S., Chao, J., Yen, J.C., Lin, L.W., Tsai, F.S., Hsieh, M.T., Peng, W.H., Cheng, H.Y. Schizandrin protects primary rat cortical cell cultures from glutamate-induced apoptosis by inhibiting activation of the MAPK family and the mitochondria dependent pathway. Molecules 18: 354-372, 2012. https://doi.org/10.3390/molecules18010354
  17. Melhem, A., Stern, M., Shibolet, O., Israeli, E., Ackerman, Z., Pappo, O., Hemed, N., Rowe, M., Ohana, H., Zabrecky, G., Cohen, R., Ilan, Y. Treatment of chronic hepatitis C virus infection via antioxidants: results of a phase I clinical trial. J Clin Gastroenterol 39: 737-742, 2005. https://doi.org/10.1097/01.mcg.0000174023.73472.29
  18. Park, E.J., Chun, J.N., Kim, S.H., Kim, C.Y., Lee, H.J., Kim, H.K., Park, J.K., Lee, S.W., So, I., Jeon, J.H. Schisandrin B suppresses TGF$\beta$1 signaling by inhibiting Smad2/3 and MAPK pathways. Biochem Pharmacol 83: 378-384, 2012. https://doi.org/10.1016/j.bcp.2011.11.002
  19. Jo, S.H., Ha, K.S., Moon, K.S., Lee, O.H., Jang, H.D., Kwon, Y.I. In vitro and in vivo anti-hyperglycemic effects of Omija (Schizandra chinensis) fruit. Int J Mol Sci 12: 1359-1370, 2011. https://doi.org/10.3390/ijms12021359
  20. Park, S.H., Han, J.H. A study of medicinal plants for applications in functional foods. 1. Effects of Schisandra fructus on the regional cerebral blood flow and blood pressure in rats. J Korean Soc Food Sci Nutr 33: 34-40, 2004. https://doi.org/10.3746/jkfn.2004.33.1.034
  21. Lee, S.H., Lee, H. A study on the effect of herbal -acupuncture with Schisandra fructus solution on hyperlipidemia in rats induced by high fat diet. The J Korean Acupuncture & Moxibustion Society 28: 143-153, 2011.
  22. Gnabre, J., Unlu, I., Chang, T.C., Lisseck, P., Bourne, B., Scolnik, R., Jacobsen, N.E., Bates, R., Huang, R.C. Isolation of lignans from Schisandra chinensis with anti-proliferative activity in human colorectal carcinoma: Structure-activity relationships. Analyt Technol 878: 2693-2700, 2010.
  23. Kim, J.H., Choi, Y.W., Park, C., Jin, C.Y., Lee, Y.J., Park, da. J., Kim, S.G., Kim, G.Y., Choi, I.W., Hwang, W.D., Jeong, Y.K., Kim, S.K., Choi, Y.H. Apoptosis induction of human leukemia U937 cells by gomisin N, a dibenzocyclooctadiene lignan, isolated from Schizandra chinensis Baill. Food Chem Toxicol 48(3):807-813, 2010. https://doi.org/10.1016/j.fct.2009.12.012
  24. Kim, B.J., Park, E.J., Lee, J.H., Jeon, J.H., Kim, S.J., So, I. Suppression of transient receptor potential melastatin 7 channel induces cell death in gastric cancer. Cancer Sci 99(12):2502-2509, 2008. https://doi.org/10.1111/j.1349-7006.2008.00982.x
  25. Guilbert, A., Gautier, M., Dhennin-Duthille, I., Haren, N., Sevestre, H., Ouadid-Ahidouch, H. Evidence that TRPM7 is required for breast cancer cell proliferation. Am J Physiol Cell Physiol 297(3):C493-502, 2009.
  26. Wykes, R.C., Lee, M., Duffy, S.M., Yang, W., Seward, E.P., Bradding, P. Functional transient receptor potential melastatin 7 channels are critical for human mast cell survival. J Immunol 179(6):4045-4052, 2007. https://doi.org/10.4049/jimmunol.179.6.4045
  27. Jiang, J., Li, M.H., Inoue, K., Chu, X.P., Seeds, J., Xiong, Z.G. Transient receptor potential melastatin 7-like current in human head and neck carcinoma cells: role in cell proliferation. Cancer Res 67(22):10929-10938, 2007. https://doi.org/10.1158/0008-5472.CAN-07-1121
  28. Abed, E., Moreau, R. Importance of melastatin-like tran\-sient receptor potential 7 and cations (magnesium, calcium) in human osteoblast-like cell proliferation. Cell Prolif 40(6):849-865, 2007. https://doi.org/10.1111/j.1365-2184.2007.00476.x
  29. Ministry of Health and Welfare. National survey of cancer patients; Analysis of national cancer survey. Seoul, Korea, 2008.
  30. Kelsey, J.L., Berowitz, G.S. Breast cancer epidemiology. Cancer Res 48: 5615-5623, 1988.
  31. Nkondjock, A., Ghadirian, P. Risk factors and risk reduction of breast cancer. Med Sci (Paris) 21: 175-180, 2005. https://doi.org/10.1051/medsci/2005212175
  32. Dorai, T., Aggarwal, B.B. Role of chemopreventive agents in cancer therapy. Cancer Lett 215: 129-140, 2004. https://doi.org/10.1016/j.canlet.2004.07.013
  33. 대한내과학회편, Harrison's 내과학, 16th, 서울, 도서출판 MIP, pp 559-567, 2006.
  34. 권은미, 정의민, 김경석, 이수경, 최원철, 윤성우. 알러젠 제거 옻나무 추출물 위주의 한방치료와 항암화학요법을 병용한 폐암 환자 2례. 대한암한의학회지 14(1):13-20, 2009.
  35. Kim, O.C., Jang, H.J. Volatile components of Schizandra chinensis Baillon. Kor J Agric Chem Biotech 39:30-36, 1994.
  36. Panossian, A., Wikman, G. Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. J Ethnopharmacol 118(2):183-212, 2008. https://doi.org/10.1016/j.jep.2008.04.020
  37. 국민건강보험공단, http://www.nhic.or.kr/portal/site/main/
  38. 이석준, 박성식, 함유근. 환자들의 정보요구가 e-Health 시스템 사용과 성과에 미치는 영향에 관한 연구: 유방암환자대상 수요자의료정보시스템을 중심으로. The Journal of information systems 22(2):105-129, 2013. https://doi.org/10.5859/KAIS.2013.22.2.105
  39. Clapham, D.E. TRP channels as cellular sensors. Nature 426(6966):517-524, 2003. https://doi.org/10.1038/nature02196
  40. Vannier, B., Zhu, X., Brown, D., Birnbaumer, L. The membrane topology of human transient receptor potential 3 as inferred from glycosylation scanning mutagenesis and epitope immunocytochemistry. J Biol Chem 273(15):8675-8679, 1998. https://doi.org/10.1074/jbc.273.15.8675
  41. Pedersen, S.F., Owsianik, G., Nilius, B. TRP channels: an overview. Cell Calcium 38(3-4):233-252, 2005. https://doi.org/10.1016/j.ceca.2005.06.028
  42. Schmitz, C., Perraud, A.L., Johnson, C.O., Inabe, K., Smith, M.K., Penner, R., Kurosaki, T., Fleig, A., Scharenberg, A.M. Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7. Cell 114: 191-200, 2003. https://doi.org/10.1016/S0092-8674(03)00556-7
  43. Aarts, M., Iihara, K., Wei, W.L., Xiong, Z.G., Arundine, M., Cerwinski, W., MacDonald, J.F., Tymianski, M. A key role for TRPM7 channels in anoxic neuronal death. Cell 115: 863-877, 2003. https://doi.org/10.1016/S0092-8674(03)01017-1
  44. Elizondo, M.R., Arduini, B.L., Paulsen, J., MacDonald, E.L., Sabel, J.L., Henion, P.D., Cornell, R.A., Parichy, D.M. Defective skeletogenesis with kidney stone formation in dwarf zebrafish mutant for trpm7. Curr Biol 15: 667-671, 2005. https://doi.org/10.1016/j.cub.2005.02.050
  45. Vriens, J., Owsianik, G., Voets, T., Droogmans, G., Nilius, B. Invertebrate TRP proteins as functional models for mammalian channels. Pflugers Arch 449: 213-226, 2004.
  46. Sahni, J., Scharenberg, A.M. TRPM7 ion channels are required for sustained phosphoinositide 3-kinase signaling in lymphocytes. Cell Metab 8: 84-93, 2008. https://doi.org/10.1016/j.cmet.2008.06.002
  47. Kim, B.J., Lim, H.H., Yang, D.K., Jun, J.Y., Chang, I.Y., Park, C.S., So, I., Stanfield, P.R., Kim, K.W. Gastroenterology 129: 1504-1517, 2005. https://doi.org/10.1053/j.gastro.2005.08.016