Induction of Apoptotic Cell Death by Sabaek-san Extract in Human Lung Cancer A549 Cells

사백산 추출물에 의한 인체 폐암세포의 Apoptosis 유도 기전에 관한 연구

  • Lee Jae Hun (Department of Biochemistry, College of Oriental Medicine, Dongeui University) ;
  • Kang Byong Ryeung (Department of Internal Medicine, College of Oriental Medicine, Dongeui University and Research Institute of Oriental Medicine) ;
  • Kam Cheol Woo (Department of Internal Medicine, College of Oriental Medicine, Dongeui University and Research Institute of Oriental Medicine) ;
  • Park Dong Il (Department of Internal Medicine, College of Oriental Medicine, Dongeui University and Research Institute of Oriental Medicine) ;
  • Choi Yung Hyun (Department of Biochemistry, College of Oriental Medicine, Dongeui University)
  • 이재훈 (동의대학교 한의과대학 생화학교실) ;
  • 강병령 (동의대학교 한의과대학 폐계내과학교실 및 한의학연구소) ;
  • 감철우 (동의대학교 한의과대학 폐계내과학교실 및 한의학연구소) ;
  • 박동일 (동의대학교 한의과대학 폐계내과학교실 및 한의학연구소) ;
  • 최영현 (동의대학교 한의과대학 생화학교실)
  • Published : 2003.04.01

Abstract

We investigated the effects of Sabaek-san (SBS) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with SBS 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 SBS treatment increased populations of apoptotic-sub G1 phase. In addition. proteolytic cleavages of poly(ADP-ribose) polymerase and β-catenin protein were observed after treatment of SBS extract. These apoptotic effects of SBS in A549 cells were associated with marked inhibition of Bcl-2 and Bel-xL mRNA in a dose-dependent manner. however the levels of Bax expression were not affected, SBS treatment also induced a proteolytic activation of caspase-3. which is believed to play a central role In the apoptotic signaling pathway. The previous and present results indicated that SBS-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. 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. https://doi.org/10.1126/science.8108732
  3. Cell. Mol. Biol. Res. v.40 Apoptosis and the cell cycle. Chiarugi, V.;Magnelli, L.;Cinelli.;Basi, G.
  4. Cancer Res. v.54 WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. EI-Deiry, W.sS.;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.;Vogel stain, B.
  5. Cell v.80 Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Miyashita, T.;Reed, J.C. https://doi.org/10.1016/0092-8674(95)90412-3
  6. 東醫寶鑑 許浚
  7. 中醫學 臨床病理 北京中醫學院編
  8. Kor. J. Oriental Physiol. Pathol. Cell cycle arrest by Sabaek-san is associated with induction of Cdk inhibitor p21 in human lung cancer A549 cells. Kang, B.R.;Oh, C.S.;Lee, J.H., Choi, Y.H.;Park, D.I.
  9. 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.
  10. Exp. Mol. Med. v.33 Research technics for the cell cycle study Choi, Y.H. https://doi.org/10.1038/emm.2001.3
  11. Int. Oncol. v.18 Apoptotic activity of novelbile 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.
  12. 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. https://doi.org/10.1074/jbc.272.45.28479
  13. Pharmacol. Ther. v.92 The machinery of programmed cell death. Zimmermann, K.C.;Bonzon, C.;Green, D.R. https://doi.org/10.1016/S0163-7258(01)00159-0
  14. Semin. Nephrol. v.18 Necrosis and apoptosis in acute renal failure. Lieberthal, W.;Koh, J.S;Levine, J.S.
  15. 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.G.
  16. 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. https://doi.org/10.1038/371346a0
  17. 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. https://doi.org/10.1016/0092-8674(95)90541-3
  18. Br. J. Surg. v.87 E-cadherin¬catenin cell-cell adhesion complex and human cancer. Wijnhoven, B.P.;Dinjens, W.N.;Pignatelli, M. https://doi.org/10.1046/j.1365-2168.2000.01513.x
  19. Acta. Gastroenterol. Belg. v.62 The role of the E-cadherinj catenin complex in gastrointestinal cancer. Debruyne, P.;Vermeulen, S.;Mareel, M.
  20. 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. 21. Choi, Y.H.;Baek, J.H.;Yoo, M.A.;Chung, H.Y.;Kim, N.D.;Kim, K.W.
  21. Nature v.391 Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Rosse, T.;Olivier, R.;Monney, L.;Rager, M.;Conus, S.;Fellay, I.;Jansen, B.;Borner, C. https://doi.org/10.1038/35160
  22. Cell v.75 Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Hockenbery, D.M.;Oltvai, Z.N.;Yin, X.M.;Milliman, e.L.;Korsmeyer, S.J. https://doi.org/10.1016/0092-8674(93)80066-N
  23. 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. https://doi.org/10.1126/science.275.5303.1132
  24. Cell Biol. Int. v.17 Multiple pathways to apoptosis. Evans, V.G. https://doi.org/10.1006/cbir.1993.1087