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Apoptosis-inducing Effects of Radix Aconiti Extract in HL-60 Cells  

Kwon, Kang-Beom (Department of Physiology, College of Oriental Medicine, Wonkwang University)
Kim, Eun-Kyung (Department of Physiology, College of Oriental Medicine, Wonkwang University)
Moon, Hyung-Cheal (Department of Acupuncture & Moxibustion, College of Oriental Medicine, Wonkwang University)
Jeong, Taek-Sang (Department Rehabilitation Medicine, College of Oriental Medicine, Wonkwang University)
Song, Yung-Sun (Department Rehabilitation Medicine, College of Oriental Medicine, Wonkwang University)
Ryu, Do-Gon (Department of Physiology, College of Oriental Medicine, Wonkwang University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.19, no.3, 2005 , pp. 677-683 More about this Journal
Abstract
The aim of this study was to investigate the apoptotic effect and its mechanism on Radix Aconiti (RA) extract in HL-60 human leukemia cell line. RA extract induced apoptosis as confirmed by discontinuous fragmentation of DNA. To clarify the mechanisms on RA extract-induced apoptosis, we examined the caspase-3, -8 enzyme activity and protein levels including Fas, FasL in HL-60 cells. Treatment with RA extracts resulted in the increase of caspase-3 enzyme activity in a time and dose-dependent manners, which was accompanied by the cleavage of poly-(ADP-ribose) polymerase (PARP). This activation of caspase-3 enzyme resulted from cleavage of procaspase-8, which was followed by increases of FasL, Fas protein expression in RA extracts-treated HL-60 cells. In conclusion, RA extract induced apoptosis of HL-60 human leukemia cell line. This results suggest that the apoptotic mechanisms of RA extract on HL-60 cells involved in FasL, Fas activation, procaspase-8 cleavage, activation of caspase-3 and cleavage of PARP. Collectively, these results suggest that RA may be a valuable agent as a anti-cancer drug.
Keywords
Radix Aconiti; aconitine; HL-60 human leukemia cell line; apoptosis; FasL; Fas; caspase-8; caspase-3; poly-(ADP-ribose) polymerase;
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1 李尙仁, 安德均, 辛民敎. 韓藥臨床應用. 서울, 成輔社. pp 225-229, 1982.
2 許浚. 東醫寶鑑. 서울, 南山堂. p 384, 446, 732, 1980.
3 Kidd, V.J. Proteolytic activities that mediate apoptosis. Annu Rev Physiol. 60, 533-573, 1998.
4 Schulte-Hermann. R, Bursch, W., Low-Baselli, A., Wagner, A., Grasl-Kraupp, B. Apoptosis in the liver and its role in hepatocarcinogenesis. Cell Biol Toxicol. 13(4-5):339-348, 1997.
5 Widmann, C., Gibson, S., Johnson, G.L. Caspase-dependent cleavage of signaling proteins during apoptosis. A turn-off mechanism for anti-apoptotic signals. J Biol Chem. 273(12):7141-7147, 1998.
6 Li. P., Nijhawan, D., Budihardjo, I., Srinivasula, S.M., Ahmad, M., Alnemri, E.S., Wang, X. Cytochrome c and dATP-dependent formation of Apaf-l/caspase-9 complex initiates an apoptotic protease cascade. Cell 91(4):479-489, 1997.
7 Wang, Z.Q., Auer, B., Stingl, L., Berghammer, H., Haidacher, D., Schweiger, M., Wagner, E. F. Mice lacking ADPRT and poly (ADP-ribosyl)ation develop normally but are susceptable to skin disease. Genes Dev. 9(5):509-520, 1995.
8 Zhivotovsky, B., Burgess, D.H., Vanags, D.M., Orrenius, S. Involvement of cellular proteolytic machinery in apoptosis. Biochem Biophys Res Commun. 230(3):481-488, 1997.
9 Schneider, P., Bodmer, J.L., Holler, N., Mattmann, C., Scuderi, P., Terskikh, A., Peitsch, M.C., Tschopp, J. Characterization of Fas (Apo-I, CD95)-Fas ligand interaction. J Biol Chem. 272(30):18827-18833, 1997.
10 Fulda, S., Los, M, Friesen, C., Debatin, K.M. Chemosensitivity of solid tumor cells in vitro is related to activation of the CD95 system. Int JCancer. 76(1):105-114, 1998.
11 Chang, L.C., Tsai, T.R., Wang, J.J., Lin, C.N., Kuo, K.W. The rhamnose moiety of solamargine plays a crucial role in triggering cell death by apoptosis. Biochem Biophys Res Commun. 242(1):21-25, 1998.
12 辛民敎. 原色臨本草學. 서울, 南山堂. pp 263-265, 1986.
13 Raff, M.C, Barros, B.A., Burne, J.F., Coles, H.S., Ishizaki, Y., Jacobson, M.D. Programed cell death and the control of cell survival: lessons from the nervous system. Science 262(5134):695-700, 1993.   DOI
14 Friesen, C., Fulda, S., Debatn, K.M. Deficient activation of the CD95 (APO-1/Fas) system in drug-resistant cells. Leukemia 11(11):1833-1841, 1997.
15 Lazebnik, Y.A., Kaufmann, S.H., Desnoyers, S., Poirier, G.G., Earnshaw, W.C. Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature. 371(6495):346-347, 1994.
16 Muzio, M., Chinnaiyan, A.M., Kischkel, F.C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, C., Bretz, J.D., Zhang, M., Gentz, R., Mann, M., Krammer, P.H., Peter, M.E., Dixit, V.M. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/ APO-l) deathinducing signaling complex. Cell 85(6):817-827, 1996.
17 Mashima, T., Naito, M., Noguchi, K, Miller, D.X., Nicholson, D.W., Tsuruo, T. Actin cleavage by CPP-32/apopain during the development of apoptosis Oncogene 14(9):1007-1012, 1997.
18 하지용, 정병업, 이선구, 유병길. 大七氣傷이 항암, 면역조절작용 및 apoptosis에 미치는 영향 동의생리병리학회지 15(1):111-124, 2001.
19 中醫大辭典輯委員會編. 中醫大蘇典(中藥分冊). 北京, 人民衛生出版社. pp 189-190, 1980.
20 Nayfield, S.G., Karp, J.E., Ford, L.G., Dorr, F.A., Kramer, B.S. Potential role of tamoxifen in prevention of breast cancer. J Natl Cancer Inst. 83(20):1450-1459, 1991.
21 류도곤, 강순수. 附子전탕액이 가토의 부신피질 및 신장기능과 혈장 Renin 활성도에 미치는 영향. 대한동의생리학회지3(2):25-48, 1989.
22 Thompson, C.B. Apoptosis in the pathogenesis and treatment of disease. Science 267(5203):1456-1462, 1995.   DOI
23 Igney, F.H., Krammer, P.H. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer 2(4):277-288, 2002.
24 Johnstone, R.W., Ruefli, A.A., Lowe, S.W. Apoptosis: a link between cancer genetics and chemotherapy. Cell 108(2):153-164, 2002.
25 Vaux, D.L. CED-4--the third horseman of apoptosis. Cell. 90(3):389-90, 1997.
26 落合英三. トリカブト 根の題基成分に就して. 日本東洋醫學會誌 19(2):1-11, 1968.
27 Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72, 248-254, 1976.
28 문구, 정병학, 김병주. 암 동서의 결합치료 1권. 익산, 원광대학교 출판국. pp 1-22, 255-258, 381-386, 413-419, 477, 448, 1998
29 Fulda, S., Sieverts, H., Friesen, C., Herr, I., Debatin, K.M. The CD95 (Apo-1/Fas) system medicated drug induced apoptosis in neuroblastoma cells. Cancer Res. 57(17):3823-3829, 1997.
30 Kastan, M.B., Canman, C.E., Leonard, C.J. P53, cell cycle control and apoptosis: implications for cancer. Cancer Metastasis Rev. 14(1):3-15, 1995.
31 Chinnaiyan, A.M., O'Rourke, K, Lane, B.R, Dixit, V.M. Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science 275(5303):1122-1126, 1997.   DOI
32 Zou, H., Henzel, W.J., Liu, X., Lutschg, A, Wang, X. Apaf-1, a human protein homologues to C elegans CED-4, participates in cytochrome codependent activation of caspase-3. Cell 90(3):405-413, 1997.
33 조선혜, 김창주, 이충렬. 흰쥐 신경세포에서 맥문동과 부자에 의해 유발된 이온전류의 특성. 대한동의생리학회지 12(2):155-164, 1997.
34 Wyllie, A.H., Kerr, J.F., Currie, A.R. Cell death: the significance of apoptosis. Int Rev Cytol 68, 251-306, 1980.
35 Kothakota, S., Azuma, T., Reinhard, C., Klippel, A., Tang, J., Chu, K., McGarry, T.J., Kirschner, M.W., Koths, K., Kwiatkowski, D.J., Williams, L.T. Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science 278(5336):294-298, 1997.   DOI
36 Guseva, N.V., Taghiyev, A.F., Rokhlin, O.W., Cohen, M.B. Contribution of death receptor and mitochondrial pathways to Fas-mediated apoptosis in the prostatic carcinoma cell line PC3. Prostate. 51(4):231-240, 2002.
37 Muller, M., Strand, S., Hug, H., Heinemann, E.M., Walczak, H., Hofmann, W.J., Stremmel, W., Krammer, P.H., Galle, P. Drug-induced apoptosis in hepatoma cells is medicated by the CD95 (APO-1/Fas) receptor/ligand system and involves activation of wild-type p53. J Clin Invest. 99(3):403-413, 1997.
38 진선두, 신상오, 양재하, 권영규, 김광중. 녹차의 주성분인 epigallocatechin gallate의 항암활성 과 apoptosis기전에 관한 분자생물학적 연구. 동의생리병리학회지 15(4):611-620, 2001.
39 Cohen, J.J. Apoptosis. Immunol Today. 14(3):126-130, 1993.