Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
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Induction of Apoptotic Cell Death by Insamsapye-tang Extract in Human Lung Cancer A549 Cells

인삼사폐탕 추출물에 의한 인체 폐암세포의 Apoptosis 유도 기전에 관한 연구

  • Park Cheol (Department of Biochemistry, and Internal Medicine, College of Oriental Medicine, Dongeui University) ;
  • Lee Min Woo (Research Institute of Oriental Medicine, College of Oriental Medicine, Dongeui University) ;
  • Kim Won Il (Research Institute of Oriental Medicine, College of Oriental Medicine, Dongeui University) ;
  • Lee Won Ho (Department of Biology, College of Natural Sciences, Busan National University) ;
  • Park Dong Il (Research Institute of Oriental Medicine, College of Oriental Medicine, Dongeui University) ;
  • Choi Yung Hyun (Department of Biochemistry, and Internal Medicine, College of Oriental Medicine, Dongeui University)
  • 박철 (동의대학교 한의과대학 생화학교실) ;
  • 이민우 (동의대학교 한의과대학 폐계내과학교실 및 한의학연구소) ;
  • 김원일 (동의대학교 한의과대학 폐계내과학교실 및 한의학연구소) ;
  • 이원호 (부산대학교 자연과학대학 생물학과) ;
  • 박동일 (동의대학교 한의과대학 폐계내과학교실 및 한의학연구소) ;
  • 최영현 (동의대학교 한의과대학 생화학교실)
  • Published : 2003.06.01
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Abstract

We investigated the effects of Insamsapye-tang (ISSPT) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with ISSPT extract, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis, including condensation of chromatin. Flow cytometry analysis confirmed that ISSPT treatment increased populations of apoptotic-sub G1 phase. In addition, proteolytic degradation of poly(ADP-ribose) polymerase (PARP) and β-catenin protein were observed after treatment of ISSPT extract. These apoptotic effects of ISSPT in A549 cells were associated with marked inhibition of Bel-xL expression in a dose-dependent manner, however the levels of Bcl-2 and Bax expression were not affected. ISSPT treatment also induced the expression of tumor suppressor p53 mRNA and inhibited the expression of caspase-3 mRNA. The previous and present results indicated that ISSPT-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis.

Keywords

References

  1. Am. J. Pathol. v.136 Apoptosis. The role of the endonuclease. Arends, M.J.;Morris, R.G.;Wyllie, A.H.
  2. Cell Biol. Int. v.17 Multiple pathways to apoptosis. Evans, V.G.
  3. Science v.263 Premature p34cdc2 activation required for apoptosis. Shi. L.;Nishioka, W.K.;Th'ng, J.;Bradbury, E.M.;Litchfield, D.W.;Greenberg, A.H.
  4. Cell. Mol. Biol. Res. v.40 Apoptosis and the cell cycle. Chiarugi, V.;Magnelli, L.;Cinelli.;Basi, G.
  5. Cancer Res. v.54 WAF1/CIPl is induced in p53-mediated G1 arrest and apoptosis. EI-Deiry, W.S.;Harper, J.W.;O'Connor, P.M.;Velculescu, V.E.;Canman, C.E.;Jackman,J.;Pietenpol,J.A.;Burrell, M.;Hill, D.E.;Wang, Y.;Wiman, K.G.;Mercer, W.E.;Kastan, M.B.;Kohn, K.W.;Elledge, S.J.;Kinzler, K.W.;Vogelstain, B.
  6. Cell v.80 Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Miyashita, T.;Reed, J.C.
  7. 國譯編註 醫學入門 v.4 安秉國(譯)
  8. 抗癌中草藥彩色圖譜 李軍德
  9. Kor. J. Oriental Physiol. Pathol. (submitted). Induction of Cdk inhibitor p27 and inhibition of pRB phosphorylation by Insamsapye-tang treatment in human lung cancer A549 cells Lee, M.W., C. Park, W.H. Lee, Y.H. Choi, D.I. Park
  10. 東醫寶鑑 許浚
  11. Kor. J. Oriental Physiol. Pathol. v.16 The effects of Yunpyesan on cell proliferation, apoptosis and cell cycle progression of human lung cancer A549 cells Kang,Y.K.;D.I.Park;J.H.Lee;Y.H.Choi
  12. Int. J. Oncol. v.21 Tetrandrine-induced cell cycle arrest and apoptosis in A549 human lung carcinoma cells. Lee, J.H.;Kang, G.H.;Kim, G.C.;Kim, K.M.;Choi, B.T.;Kang, H.S.;Lee, Y.T.;Choi, Y.H.
  13. Exp. Mol. Med. v.33 Research technics for the cell cycle study Choi, Y.H.
  14. Int. J. Oncol. v.18 Apoptotic activity of novel bile acid derivatives in human leukemic T cells through the activation of caspases. Choi, Y.H.;Im, E.O.;Suh, H.S.;Jin, Y.E.;Lee, W.H.;Yoo, Y.H.;Kim, K.W.;Kim, N.D.
  15. J. Biol. Chem. v.272 Regulation of cyclin D1 by calpain protease. Choi, Y.H.;Lee, S.J.;Nguyen, P.;Jang, J.S.;Lee, J.;Wu, M.L.;Takano, E.;Maki, M.;Henkart, P.A.;Trepel, J.B.
  16. Kor. J. Oriental Physiol. Pathol. (submitted). Induction of apoptotic cell death by sabaeksan extract in human lung cancer. A549 cells Lee, J.H.;B.R.Kang;C.W.Kam;D.I.Park;Y.H.Choi
  17. Pharmacol. Ther. v.92 The machinery of programmed cell death. Zimmermann, K.C.;Bonzon, C.;Green, D.R.
  18. Semin. Nephrol. v.18 Necrosis and apoptosis in acute renal failure. Lieberthal, W.;Koh, J.S.;Levine, J.S.
  19. Cancer Res. v.53 Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Kaufmann, S.H.;Desnoyers, S.;Ottaviano, Y.;Davidson, N.E.;Poirier, G.C.
  20. Nature v.371 Cleavage of poly ADP-ribose polymerase by a proteinase with properties like ICE. Lazebnik, Y.A.;Kaufmann, S.H.;Desnoyers, S.;Poirier, G.G.;Earnshaw, W.C.
  21. Cell v.81 Yama/CPP32, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Tewari, M.;Quan, L.T.;O'Rourke, K.;Desnoyers, S.;Zeng, Z.;Beidler, D.R.;Poirier, G.G.;Salvesen, G.S.;Dixit, V.M.
  22. Br. J. Surg. v.87 E-cadherin-catenin cell-cell adhesion complex and human cancer. Wijnhoven, B.P.;Dinjens, W.N.;Pignatelli, M.
  23. Acta. Gastroenterol. Belg. v.62 The role of the E-cadherin/catenin complex in gastrointestinal cancer. Debruyne, P.;Vermeulen, S.;Mareel, M.
  24. Int. J. Oncol. v.17 Induction of apoptosis by ursolic acid through activation of caspases and down-regulation of c-IAPs in human prostate epithelial cells. Choi, Y.H.;Baek, J.H.;Yoo, M.A.;Chung, H.Y.;Kim, N.D.;Kim, K.W.
  25. Nature v.391 Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Rosse, T.;O1ivier, R.;Monney, L.;Rager, M.;Conus, S.;Fellay, I.;Jansen, B.;Boner, C.
  26. Cell v.75 Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Hockenbery, D.M.;Oltvai, Z.N.;Yin, X.M.;Milliman, C.L.;Korsmeyer, S.J.
  27. Science v.275 The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Kluck, R.M.;Bossy-Wetzel, E.;Green, D.R.;Newmeyer, D.D.
  28. Annu. Rev. Med. v.53 Cyclooxygenase-2: a therapeutic target. Turini, M.E.;DuBois, R.N.
  29. Best Pract. Res. Clin. Gastroenterol. v.15 COX-2 inhibition and prevention of cancer. Giercksky, K.E.
  30. Int. J. Cancer v.94 Is COX-2 inhibition a panacea for cancer prevention? Vainio, H.
  31. J. Cancer Res. Clin. Oncol. v.127 Cyclooxygenase-2: a novel target for cancer chemotherapy? Dempke, W.;Rie, C.;Grothey, A.;Schmoll, H.J.
  32. Mutat. Res. v.480;481 Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals:down-regulation of COX-2 and iNOS through suppression of NF-kB activation. Surh, Y.J.;Chun, K.S.;Cha, H.H.;Han, S.S.;Keum, Y.S.;Park, K.K.;Lee, S.S.
  33. Int. J. Mol. Med. v.2 Cox-2, iNOS and p53 as play-makers of tumor angiogenesis. Chiarugi V.;Magnelli, L.;Gallo, O.
  34. Lab. Invest. v.79 Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo. Sawaoka, H.;Tsuji, S.;Tsujii, M.;Gunawan, E.S.;Sasaki, Y.;Kawano, S.;Hori, M.
  35. J. Natl. Cancer Inst. v.94 Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. Thun, M.J.;Henley, S.J.;Patrono, C.