항백탕 추출물의 인간 백혈병 세포주 HL-60에서 항백혈병 효과

Anti-leukemic Effects of Hwoangbaec-tang in Human Promyelocytic Leukaemia, HL-60 Cells

  • 김용준 (원광대학교 의과대학 미생물학 및 면역학교실) ;
  • 전병훈 (원광대학교 한의과대학 병리학교실) ;
  • 주성민 (원광대학교 한의과대학 병리학교실) ;
  • 이장천 (상지대학교 한의과대학) ;
  • 박양구 (원광대학교 한의과대학 방제학교실) ;
  • 이상현 (원광대학교 한의과대학 방제학교실) ;
  • 전영균 (원광대학교 한의과대학 방제학교실) ;
  • 황주민 (원광대학교 한의과대학 방제학교실) ;
  • 임대환 (원광대학교 한의과대학 방제학교실) ;
  • 윤용갑 (원광대학교 한의과대학 방제학교실)
  • Kim, Young-Jun (Department of Microbiology and Immunology, Wonkwang University) ;
  • Jeon, Byung-Hun (Department of Pathology, College of Oriental Medicine, Wonkwang University) ;
  • Ju, Sung-Min (Department of Pathology, College of Oriental Medicine, Wonkwang University) ;
  • Lee, Jang-Chun (Department of Prescription, College of Oriental Medicine, Sangji University) ;
  • Park, Yang-Koo (Department of Prescription, College of Oriental Medicine, Wonkwang University) ;
  • Lee, Sang-Hyun (Department of Prescription, College of Oriental Medicine, Wonkwang University) ;
  • Chon, Young-Gyun (Department of Prescription, College of Oriental Medicine, Wonkwang University) ;
  • Hwang, Joo-Min (Department of Prescription, College of Oriental Medicine, Wonkwang University) ;
  • Lim, Dae-Hwan (Department of Prescription, College of Oriental Medicine, Wonkwang University) ;
  • Yun, Young-Gab (Department of Prescription, College of Oriental Medicine, Wonkwang University)
  • 발행 : 2005.06.25

초록

The composition of Hwoangbaec-tang has been traditionally used in Korea to treat cancer. Hwoangbaec-tang I is the water extracts prepared from Angelica dahurica, Fritillariae verticillata, Ailanthus altissima, Viscum coloratun, Scutellaria Radix, Ginseng Radix, Astragalus membranaceus, and Glycyrrhizae Radix. Hwoangbaec-tang II also is the water extracts prepared from Ginseng Radix, Astragalus membranaceus, and Glycyrrhizae Radix. The anti-leukemic effects of human promyelocytic leukaemia (HL-60 cells) by Hwoangbaec-tang I or II was accessed by propidium iodide staining flow cytometric analysis, and apoptosis-inducing activity was further confirmed by a nuclear morphological change, a ladder pattern of DNA fragmentation, and an activation of caspase-3 and 9. Hwoangbaec-tang I was found to induce the apoptosis of HL-60 cells via caspase-3 and 9 pathway. In the other side, Hwoangbaec-tang II was found to inhibit the growth of HL-60 cells by inducing these cells to differentiate toward granulocytes. These results indicate that the different anti-leukemic effects of Hwoangbaec-tang in HL-60 cells can be induce the apoptosis or differnetiation of HL-60 cells in Hwoangbaec-tang composition dependent manner.

키워드

참고문헌

  1. Panchal, R.G. Novel therapeutic strategies to selectively kill cancer cells. Biochem Pharmacol. 55, 247-252, 1998.
  2. Smets, L.A. Programmed cell death (apoptosis) and response to anti-cancer drugs. Anticancer Drugs 5, 3-9, 1994.
  3. Watson, A.J. Review article: manipulation of cell death-the development of novel strategies for the treatment of gastrointestinal disease. Aliment Pharmacal Ther. 9, 215-226, 1995.
  4. Nicotera, P., Leist, M., Ferrando-May, E. Apoptosis and necrosis: different execution of the same death. Biochem Soc Symp. 66, 69-73, 1999.
  5. Vermes, I., Haanen, C, Reutelingsperger, C. Flow cytometry of apoptotic cell death. J Immunol Methods 243, 167-190, 2000.
  6. Loo, D.T., Rillema, J.R. Measurement of cell death. Methods Cell Biol. 57, 251-264, 1998.
  7. Allen, R.T., Hunter, W.J. 3rd., Agrawal DK. Morphological and biochemical characterization and analysis of apoptosis. J Pharmacol Toxicol Methods 37, 215-228, 1997.
  8. Matsuda, S., Minowa, A, Suzuki, S., Koyasu, S. Differential activation of c-Jun NH2-terminal kinase and p38 pathways during FTY720-induced apoptosis of T lymphocytes that is suppressed by the extracellular signal-regulated kinase pathway. J Immunol. 162, 3321-3326, 1999.
  9. Zheng, S., Yang, H., Zhang, S., Wang, X., Yu, L., Lu, J., Li, J. Erratum. J Cell Biochem. 77, 125, 2000.
  10. Oh, G.S., Hong, K.H., Oh, H., Pae, H.O., Kim, I.K., Kim, N.Y., Kwon, T.O., Shin, M.K., and Chung, H.T. 4-Acetyl-12,13-epoxyl-9-trichothecene-3,15-diol isolated from the fruiting bodies of Isariajaponica Yasuda induces apoptosis of human leukemia cells (HL-60). Biol Pharm Bull. 24, 785-789, 2001.
  11. 배현옥, 임창경, 장선일, 한동민, 안원근, 윤유식, 전병훈, 김원신, 윤용갑. 항 백혈병 작용에 관련된 천연물의 자료 조사. 동의생리병리학회지, 17, 605-610, 2003.
  12. Pae, H.O., Oh, H., Choi, B.M., Oh, G.S., Paik, S.G, Jeong, S., Hwang, K.M., Yun, Y.G, Chung, H.T. Differentiation-inducing effects of verticinone, an isosteroidal alkaloid isolated from the bulbus of Fritillaria ussuriensis, on human promyelocytic leukemia HL-60 cells. Bioi Pharm sun. 25, 1409-411, 2002.
  13. Pae, H.O., Oh, H., Yun, Y.G., Oh, G.S., Jang, S.I., Hwang, KM., Kwon, T.O., Lee, H.S., Chung, H.T. mperatorin, a furanocoumarin from Angelica dahurica (Umbelliferae), induces cytochrome c-dependent apoptosis in human promyelocytic leukaemia, HL-60 Cells. Pharmacol Toxicol.,91, 40-48, 2002.
  14. Wang, J., Yu, Y., Hashimoto, F., Sakata, Y., Fujii, M., Hou, D.X. Baicalein induces apoptosis through ROS-mediated mitochondrial dysfunction pathway in HL-60 cells. Int J Mol Med., 14, 627-632, 2004.
  15. Kim, Y.S., Jin, S.H. Ginsenoside Rh2 induces apoptosis via activation of caspase-1 and -3 and up-regulation of Bax in human neuroblastoma. Arch Pharm Res., 27, 834-839, 2004.
  16. Mori, H., Niwa, K, Zheng, Q., Yamada, Y., Sakata, K, Yoshimi, N. Cell proliferation in cancer prevention; effects of preventive agents on estrogen-related endometrial carcinogenesis model and on an in vitro model in human colorectal cells. Mutat Res., 480-481, 201-207, 2001.
  17. Lian, Z., Niwa, K, Gao, J., Tagami, K, Mori, H., Tamaya, T. Association of cellular apoptosis with anti-tumor effects of the Chinese herbal complex in endocrine-resistant cancer cell line. Cancer Detect Prev, 27, 147-154, 2003.
  18. Yang, J.H., Chou, C.C., Cheng, Y.W., Sheen, L.Y., Chou, M.C, Yu, H.S., Wei, Y.H., Chung, J.G. Effects of glycolic acid on the induction of apoptosis via caspase-3 activation in human leukemia cell line (HL-60). Food Chern Toxicol., 42, 1777-1784, 2004.
  19. Roush, W.R., Hagadorn, S.M. Synthesis of mycarose and epi-axenose from non-carbohydrate precursors. Carbohydr Res. 136, 187-193, 1985.
  20. Shimizu, C, Li, X., Kimura, M., Hashimoto, K., Sugaya, K., Kubo, M., Suzuki, S., Nakayama, T. A novel immunosuppressant, FTY720, increases the efficiency of a superantigen-induced peripheral T-cell deletion whilst inhibiting negative selection in the thymus. Immunology 94, 503-512, 1998.
  21. Blagosklonny, M.V. Cell death beyond apoptosis. Leukemia. 14, 1502-1508, 2000.
  22. Counis, M.F., TorrigIia, A. DNases and apoptosis. Biochem Cell Biol. 78, 405-414, 2000.
  23. Mak, T.W., Yeh, W.C. Signaling for survival and apoptosis in the immune system. Arthritis Res. Suppl 3, S243-252, 2002.
  24. Truong-Tran, A.Q., Carter, J., Ruffin, R.E., Zalewski, P.D. The role of zinc in caspase activation and apoptotic cell death. Biometals. 14, 315-330, 2001.
  25. Claridge, C.A., Schmitz, H., Bradner, W.T. Antitumor activity of some microbial and chemical transformation products of anguidine (4,15-diacetoxyscirpene-3-ol). Cancer Chemother Pharmacol. 2, 181-182, 1979.
  26. Shifrin, V.I., Anderson, P. Trichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis, J Bioi Chem. 274, 13985-13992, 1999.
  27. Tsiftsoglou, A.S., Pappas, I.S., Vizirianakis, I.S. Mechanisms involved in the induced differentiation of leukemia cells. Pharmacol Ther. 100, 257-290, 2003.