동의생리병리학회지 (Journal of Physiology & Pathology in Korean Medicine)

  • 제20권6호
  • /
  • Pages.1548-1555
  • /
  • 2006
  • /
  • 1738-7698(pISSN)
  • /
  • 2288-2529(eISSN)
대한동의생리학회·한의병리학회 ( The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine)
권호 표지

인간 신경모세포종 세포주 LAN5에 대한 부정항암탕(扶正抗癌湯)의 항종양효과

Anti-cancer Effects of Bujeonghangam-tang on Human Neuroblastoma Cell Line LAN5

  • 조영기 (원광대학교 전주 한방병원) ;
  • 이성균 (원광대학교 전주 한방병원) ;
  • 이정섭 (원광대학교 전주 한방병원) ;
  • 남상규 (원광대학교 전주 한방병원) ;
  • 정현애 (익산 한방병원) ;
  • 문구 (원광대학교 전주 한방병원) ;
  • 문미현 (원광대학교 전주 한방병원)
  • Cho, Young-Kee (Wonkwang University Jeonju Oriental Medicine Hospital) ;
  • Lee, Seong-Kyun (Wonkwang University Jeonju Oriental Medicine Hospital) ;
  • Lee, Jung-Sup (Wonkwang University Jeonju Oriental Medicine Hospital) ;
  • Nam, Sang-Kyu (Wonkwang University Jeonju Oriental Medicine Hospital) ;
  • Jeong, Hyun-Ae (Wonkwang University Iksan Oriental Medicine Hospital) ;
  • Moon, Goo (Wonkwang University Jeonju Oriental Medicine Hospital) ;
  • Moon, Mi-Hyun (Wonkwang University Jeonju Oriental Medicine Hospital)
  • 발행 : 2006.12.25
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Bujeonghangam-tang(BHT) has been used as an anticancer agent in oriental medicine, but the mechanism by which it induces cell death in cancer cells is still unclear. To investigate cell death mechanism by BHT in cancer cells, the activities of apoptosis signaling pathway were tested in human neuroblastoma cell line LAN5. Viability of LAN5 cells was markedly decreased by treatment of the water extract of BHT in a dose-dependent manner. BHT induced cell death was confirmed as apoptosis characterized by chromatin condensation. We tested whether the water extract of BHT affects the anti-apoptotic protein such as Bcl-2 and Bcl-XL, and the pro-apoptotic protein such as Bax. Both Bcl-2 and Bcl-XL were gradually decreased but Bas was increased in a time-dependent manner after the addition of the water extract of BHT. Cleavage of Bid by activation of caspase-8 protease was also observed in LAN-5 cells by the treatment of the water extract of BHT. Taken together, these results suggest that the water extract of BHT exerts anti-cancer effects on human neuroblastoma LAN-5 cells by inducing the apoptotic death via down-regulation of anti-apoptotic proteins such as Bcl-2 and Bcl-XL, up-regulation of pro-apoptotic protein such as Bax, and activation of intrinsic caspase cascades.

키워드

참고문헌

  1. 서울대학교 의과대학. 腫瘍學. 서울대학교 출판부, pp 1-3, 23-24, 26-43, 137-143, 225-234, 1992
  2. 余桂淸. 歷代中醫腫瘤案論選粹. 北京, 北京出版社, pp 1-2, 1988
  3. 王洪圖. 黃帝內經素問. 春秋出版社, p 71, 237, 271, 1988
  4. 金定濟. 東醫臨床要覽. 서울, 書苑堂, pp 253-254, 1981
  5. 上海中醫學院. 中醫外科學. 香港, 商務印書館, pp 301-307, 239-164, 1994
  6. 郞偉君. 抗癌中藥一千方. 北京, 中國醫藥技術出版社, pp 5-17, 1994
  7. 崔昇勳. 東醫腫瘍學. 서울, 杏林出版社, pp 9, 19-100, 1995
  8. 大韓病理學會 編. 病理學. 서울, 高文社, p 225, 1990
  9. 공격덕, 이상욱, 한병훈, 서승연, 허만하, 박병채. 진행성 위암에 대한 5-FU, Adriamycin 및 Cisplatin(FAC) 병용화학요법의 치료효과. 대한암학회지 22: 144, 1990
  10. KURT, J. ISSELBACHER 外. HARRISON'S PRINCIPLES OF INTERNAL MEDICINE Thirteenth Edition Volume 2, United States of America, Monotype Composition Company, pp 1814-1815, 1826-1840, 1817-1821, 1994
  11. 李家康. 中醫腫瘤防治大全. 中國, 科學技術文獻出版社, pp 10-47, 76-103, 142-150, 1994
  12. 문구. 정병학, 김병주 편저. 암 동서의 결합치료. 권1, pp. 72-92, 93-98, 256-257, 1999
  13. Fadeel, B., Henter, J.I., Orrenius, S. Apoptosis required for maintenance of homeostasis: familial hemophagocytic lymphohitiocytosis caused by too little cell death Lakartidningen. 97:1395-1400, 1402, 2000
  14. Mesner, P., Budihardjo, I., Kaufmann, S.H. Chemotherapy- induced apoptosis. Adv. Pharmacol. 41:461, 1997
  15. Dai, J., Weinberg, S.R., Waxman, S., Jing, Y. Maligment cells can ge sensitixed to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glultathione redox system. Blood. 93:268-277. 1999
  16. Huang, S., Huang, C.F., Lee, T. Induction of mitosis- mediated apoptosis by sodicum arsenite in HeLa S3 cells. Biochem Pharmacol. 60:771-780. 2000 https://doi.org/10.1016/S0006-2952(00)00397-X
  17. Desagher, S., Martinou, J.C. Mitochondria as the central control point of apoptosis, Trends Cell Biol, 10(9):369-377, 2000 https://doi.org/10.1016/S0962-8924(00)01803-1
  18. Sasaki, S. Antitumor agents from medical plants, Jpn. Kokai Tokyo koho Jp, pp 58-118, 1983
  19. Tang Defang, Hao Yohung, Liu Zuoya, Miao Shulin, Wei Hua, Wu Jian. Constituents of the essential oil from rhizome of Attactylodes macrocephala produced in pingjiang (China) and their antitumor effects, Yaoxue Tongbao, 19(9):555-558. 1984
  20. 노훈정. 消積補中丸의 抗腫瘍效果에 관한 實驗的 硏究. 익산, 원광대학교 대학원, 1995
  21. 신민교. 臨床本草學. 서울, 永林社, pp 172-173, 179-183, 188-191, 194-196, 211-212, 236-239, 255-260, 279-280, 469-472, 479-480, 480-481, 567-568, 569-570, 576-577, 585-588, 593-594, 668-669, 688-689, 819-821, 1997
  22. 金柄住. 扶正抗癌湯의 抗腫瘍효과에 관한 실험적 硏究. 益山, 원광대학교 대학원, 1997
  23. 尹泳大. 扶正抗癌湯이 마우스의 체액성 및 세포성 면역반응과 탐식세포기능에 미치는 영향. 익산, 원광대학교 대학원, 1997
  24. 林美良. 扶正抗癌湯이 抗腫瘍 면역반응에 미치는 영향. 익산, 원광대학교 대학원, 1997
  25. 崔云榮. 扶正抗癌湯이 抗癌작용 및 면역기능에 미치는 영향. 익산, 원광대학교 1999
  26. 金完熙, 崔達永. 臟腑辨證論治. 서울, 成輔社, pp 140-142, 168-170, 281-284, 1985
  27. 錢伯文. 腫瘤的辨證施治. 上海, 上海科學技術出版社, pp 1-10, 1980
  28. Searle, J., Kerr, J.F.R., Bishop, C.J. Necrosis and apoptosis: distinct modes of cell death with fundamentally different significance, Pathol. Annu, 17:229-259, 1982
  29. Klaus, S.O., Davide, F. Apoptosis signal by death receptors, Eur. J. Biochem, 254:439-459. 1998 https://doi.org/10.1046/j.1432-1327.1998.2540439.x
  30. Raff, M.C., Bares, B.A., Burne, J.F., Coles, H.S., Ishizaki, Y., Jacobson, M.D. Programed cell death and the control of cell survival. Science 262:695-700, 1993 https://doi.org/10.1126/science.8235590
  31. Scott, H.K., William, C.E. Induction of apoptosis by cancer chemotherapy. Experimental Cell Research, 256:42-49, 2000 https://doi.org/10.1006/excr.2000.4838
  32. Freisen, C., Herr, I., Krammer, P.H., Debatin, K.M. Invovement of the CD95 (APO-1/Fas) receptor/ligand system in drug-induced apoptosis in Leukemia cells. Nature Med. 2: 574-577, 1996 https://doi.org/10.1038/nm0596-574
  33. Green, D.R., Reed, J.C. Mitochondria and apoptosis. Science, 281:1309-1312, 1998 https://doi.org/10.1126/science.281.5381.1309
  34. Yang, J., Lui, X., Bhalla, K., Kim, C.N., Ibrado, A.M., Cai, J., Peng, T.I., Jones, D.P., Wang, X. Prevention of apoptosis by Bcl-2: realease of cytochrome c frome mitochondria blocked. Science, 275:1129-1132, 1997 https://doi.org/10.1126/science.275.5303.1129
  35. Kim, C.N., Wang, X., Huang, A.M., Liu, I., Fang, G., Bhalla, K. Overexpression of Bcl-xL inhibits Ara-C-induced mitochondrial loss of cytochrome c and other pertubations that activate the molecular cascade of apoptosis. Cancer Res, 57:3115, 1997
  36. Kharbanda, S. et al. Role for Bcl-xL as an inhibitor of cytosolic cytochrome c accumulation in DNA damage-induced apoptosis. Proc. Natl Acad. Sci, USA, 94:6939-6942, 1997
  37. Mattew, G., Vander Heiden, Navdeep, S.C., Edward, K.W., Paul, T.S. Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria, 91:627-637, 1997 https://doi.org/10.1016/S0092-8674(00)80450-X
  38. Shigeomi S., Masashi N., Yoshihide T. : Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC, Nature 399:483-487, 1999 https://doi.org/10.1038/20959
  39. Shimizu S., Narita M., Tsujimoto Y. : Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC, Nature 399:411-412, 1999 https://doi.org/10.1038/20804
  40. Adams J.M., Cory S. : The Bcl-2 protein family: arbiters of cell survival, Science 281:1322-1326, 1998 https://doi.org/10.1126/science.281.5381.1322
  41. Kluck, R.M., Martin, S.J., Hoffman, B.M., Zhou, J.S., Green, D.R., Newmeyer, D.D. Cytochrome c activation of CPP32-like proteplysis plays a critical role on a Xenopus cell-free apoptosis system, 1997
  42. Talanian, R.V., et al. Substrate specificities of caspase family protease, J. Biol. Chem., 272:9677-9682, 1997 https://doi.org/10.1074/jbc.272.15.9677
  43. Enari, M., Talanian, R.V., Wong, W.W., Nagata, S. Sequential activation of ICE-like and CPP32-like protease during Fas-mediated apoptosis, Nature 380:723-726. 1996 https://doi.org/10.1038/380723a0
  44. Widmann, C., Gibson, S. Caspase-dependent Cleavage of signaling proteins during apoptosis. J. Biol. Chem. 273(12):7141-7147, 1998 https://doi.org/10.1074/jbc.273.12.7141
  45. Mesner, P., Budihardjo, I., Kaufmann, S.H. Chemotherapy- induced apoptosis. Adv. Pharmacol. 41:461, 1997. https://doi.org/10.1016/S1054-3589(08)61069-8
  46. Thomson, C.B. Apoptosis in the pathogenesis and treatment of disease. Science 267:1456-1462, 1995 https://doi.org/10.1126/science.7878464
  47. 劑春安. 抗癌中草藥大辭典. 中國, 湖北科學技術出版社, pp 14-23, 33-35, 80-84, 115-119, 260-265, 294-297, 340-344, 367-371, 392-398, 398-401, 440-447, 538-543, 565-570, 704-708, 721-724, 817-820, 903-908, 1102-1104, 1994