동의생리병리학회지 (Journal of Physiology & Pathology in Korean Medicine)

  • 제21권6호
  • /
  • Pages.1513-1519
  • /
  • 2007
  • /
  • 1738-7698(pISSN)
  • /
  • 2288-2529(eISSN)
대한동의생리학회·한의병리학회 ( The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine)
권호 표지

육울탕(六鬱湯)에 의한 인체자궁경부암세포의 증식억제에 관한 연구

Induction of Apoptosis by Yukwool-tang in Human Cervical Carcinoma HeLa Cells

  • 최영현 (동의대학교 한의과대학 생화학교실, 대학원 바이오물질제어학과) ;
  • 최병태 (부산대학교 한의학전문대학원 해부학교실) ;
  • 이용태 (한의과대학 생리학교실)
  • Choi, Yung-Hyun (Department of Biochemistry, College of Oriental Medicine and Department of Biomaterials Control, Graduate School) ;
  • Choi, Byung-Tae (Department of Anatomy, Graduate School of Oriental Medicine, Pusan National University) ;
  • Lee, Yong-Tae (Department of Physiology, College of Oriental Medicine, Dongeui University)
  • 발행 : 2007.12.25
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Yukwool-tang (YWT) is a traditional Chinese medicine, which has been used for patients suffering from a uterine disease in Oriental medicine. In the present study, it was examined the biochemical mechanisms of apoptosis by YWT in human cervical carcinoma HeLa cells. It was found that YWT could inhibit the cell growth of HeLa cells in a dose-dependent manner, which was associated with apoptotic cell death such as formation of apoptotic bodies and DNA fragmentation. Flow cytometry analysis confirmed that YWT treatment increased populations of apoptotic-sub-G1 phase of the cell cycle. We observed the p53-independent induction of p21 proteins, down-regulation of anti apoptotic Bcl-2 expression and proteolytic activation of caspase-3 in YWT-treated HeLa cells. YWT treatment also concomitant degradation and/or inhibition of poly (ADP-ribose) polymerase (PARP), phospholipase C-1 ($PLC{\gamma}1$), ${\beta}-catenin$ and DNA fragmentation factor 45/inhibitor of caspase-activated DNase (DFF45/ICAD). Taken together, these findings partially provide novel insights into the possible molecular mechanism of the anti-cancer activity of YWT.

키워드

참고문헌

  1. Arends, M.J., Morris, R.G., Wyllie, A.H. Apoptosis. The role of the endonuclease. Am. J. Pathol. 136: 593-608, 1990
  2. Evans, V.G. Multiple pathways to apoptosis. Cell Biol. Int. 17: 461-476, 1993 https://doi.org/10.1006/cbir.1993.1087
  3. Shi, L., Nishioka, W.K., Th'ng, J., Bradbury, E.M., Litchfield, D.W., Greenberg, A.H. Premature p34cdc2 activation required for apoptosis. Science 263: 1143-1145, 1994 https://doi.org/10.1126/science.8108732
  4. Chiarugi, V., Magnelli, L., Cinelli, M., Basi, G. Apoptosis and the cell cycle. Cell. Mol. Biol. Res. 40: 603-612, 1994
  5. El-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., Vogelstain, B. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res. 54: 1169-1174, 1994
  6. 공신, 고금의감, 남창, 강서과학기술출판사, p 99, 1990
  7. 이천, 원본편주의학입문, 서울, 대성문화사, p 358, 563, 564, 1989
  8. Lee, Y.T., Choi, B.T., Choi, Y.H., Kang, K.H. Development of health assistances for anti-stress used with Ostreae concha. Kor. J. Ori. Physiol. Pathol. 20: 1604-1611, 2006
  9. Harper, J.W., Adami, G.R., Wei, N., Keyomarsi, K., Elledge, S.J. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75: 805-816, 1993 https://doi.org/10.1016/0092-8674(93)90499-G
  10. Xiong, Y., Hannon, G., Zhang, H., Casso, D., Kobayashi, R., Beach, D. p21 is a universal inhibitor of cyclin kinases. Nature 366: 701-704, 1993 https://doi.org/10.1038/366701a0
  11. Elledge, S.J., Harper, J.W. Cdk inhibitors: on the threshold of checkpoints and development. Curr. Opin. Cell Biol. 6: 847-852, 1994 https://doi.org/10.1016/0955-0674(94)90055-8
  12. Miyashita, T., Reed, J.C. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80: 293-299, 1995 https://doi.org/10.1016/0092-8674(95)90412-3
  13. Morgan, D.O. Principles of CDK regulation. Nature 374: 131-134, 1995 https://doi.org/10.1038/374131a0
  14. Reed, J.C. Bcl-2 family proteins. Oncogene 17: 3225-36, 1998 https://doi.org/10.1038/sj.onc.1202591
  15. Vegran, F., Boidot, R., Oudin, C., Riedinger, J.M., Lizard Nacol, S. Implication of alternative splice transcripts of caspase-3 and survivin in chemoresistance Bull. Cancer 92: 219-226, 2005
  16. Kaufmann, S.H., Desnoyers, S., Ottaviano, Y., Davidson, N.E., Poirier, G.G. Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Res. 53: 3976-3985, 1993
  17. Tewari, M., Quan, L.T., O'Rourke, K., Desnoyers, S., Zeng, Z., Beidler, D.R., Poirier, G.G., Salvesen, G.S., Dixit, V.M. Yama/CPP32, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell 81: 801-809, 1995 https://doi.org/10.1016/0092-8674(95)90541-3
  18. Fukuda, K. Apoptosis-associated cleavage of $\beta$-catenin in human colon cancer and rat hepatoma cells. Int. J. Biochem. Cell. Biol. 31: 519-529, 1999 https://doi.org/10.1016/S1357-2725(98)00119-8
  19. Steinhusen, U., Badock, V., Bauer, A., Behrens, J., Wittman- Liebold, B., Dorken, B., Bommert, K. Apoptosis-induced cleavage of $\beta$-catenin by caspase-3 results in proteolytic fragments with reduced transactivation potential. J. Biol. Chem. 275: 16345-16353, 2000 https://doi.org/10.1074/jbc.M001458200
  20. Rhee, S.G., Suh, P.G., Ryu, S.H., Lee, S.Y. Studies of inositol phospholipid-specific phospholipase C. Science 244: 546-550, 1989
  21. Bae, S.S., Perry, D.K., Oh, Y.S., Choi, J.H., Galadari, S.H., Ghayur, T., Ryu, S.H., Hannun, Y.A., Suh, P.G. Proteolytic cleavage of phospholipase C-gamma1 during apoptosis in Molt-4 cells. FASEB J. 14: 1083-1092, 2000 https://doi.org/10.1096/fasebj.14.9.1083
  22. Widlak, P., Garrard, W.T. Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and endonuclease G. J. Cell. Biochem. 94: 1078-1087, 2005 https://doi.org/10.1002/jcb.20409
  23. Nagata, S. Apoptotic DNA fragmentation. Exp. Cell Res. 256: 12-18, 2000 https://doi.org/10.1006/excr.2000.4834
  24. Sheikh, M.S., Huang, Y. Death receptors as targets of cancer therapeutics. Curr. Cancer Drug Targets 4: 97-104, 2004 https://doi.org/10.2174/1568009043481597
  25. Klas, C., Debatin, K.M., Jonker, R.R., Krammer, P.H. Activation interferes with the APO-1 pathway in mature human T cells. Int. Immunol. 5: 625-630, 1993 https://doi.org/10.1093/intimm/5.6.625
  26. Osford, S.M., Dallman, C.L., Johnson, P.W., Ganesan, A., Packham, G. Current strategies to target the anti-apoptotic Bcl-2 protein in cancer cells. Curr. Med. Chem. 11: 1031-1039, 2004 https://doi.org/10.2174/0929867043455486
  27. Rosse, T., Olivier, R., Monney, L., Rager, M., Conus, S., Fellay, I., Jansen, B., Borner, C. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature 391: 496-499, 1998 https://doi.org/10.1038/35160