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인체 혈구암세포에 대한 丹仙湯 추출물의 증식억제 및 세포사멸 유도에 관한 연구

Anti-proliferative and Pro-apoptic Effects of Dan-Seon-Tang in Human Leukemia Cells

홍상훈|박상은|김성환
대한한방내과학회 (The Society Of Korean Oriental Internal Medicine)|2011.12|대한한방내과학회지 (The Journal of Korean Oriental Internal Medicine)|제32권 제4호|pp. 565-583

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키워드

apoptosisSalviae miltiorrhizae RadixAgrimonia pilosa Ledebhuman leukemiaCodonopsis pilosula(Fr.) Nannf
주제분류한의학

초록

Objectives : This study investigated the biochemical mechanisms of anti-proliferative and pro-apoptotic effects of the water extract of Dan-Seon-Tang (DST) in human leukemia U937 cells. Methods : U937 cells were exposed to DST and growth inhibition was measured by MTT assay. Results : Exposure of U937 cells to DST resulted in the growth inhibition in a concentration-dependent manner. This inhibitory effect was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies, increased populations of apoptotic-sub G1 phase and induction of DNA fragmentation. The induction of apoptotic cell death in U937 cells by DST was associated with up-regulation of death receptor 4 (DR4) and down-regulation of Bid, surviving and cellular inhibition of apoptosis protein-2 (cIAP-2) expression. DST treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant degradation of caspase-3 substrate proteins such as poly (ADP-ribose) polymerase (PARP), phospholipase (PLC)-γ1, β-catenin and DNA fragmentation factor 45/inhibotor of caspase activated DNAse (DFF45/ICAD). Furthermore, apoptotic cell death by DST was significantly inhibited by caspase-3 specific inhibitor z-DEVD-fmk, demonstrating the important role of caspase-3. Conclusions : These findings suggest that herb prescription DST may be a potential chemotherapeutic agent for the control of human leukemia U937 cells; further study is needed to identify the active compounds.

Abstract

Objectives : This study investigated the biochemical mechanisms of anti-proliferative and pro-apoptotic effects of the water extract of Dan-Seon-Tang (DST) in human leukemia U937 cells. Methods : U937 cells were exposed to DST and growth inhibition was measured by MTT assay. Results : Exposure of U937 cells to DST resulted in the growth inhibition in a concentration-dependent manner. This inhibitory effect was associated with morphological changes and apoptotic cell death such as formation of apoptotic bodies, increased populations of apoptotic-sub G1 phase and induction of DNA fragmentation. The induction of apoptotic cell death in U937 cells by DST was associated with up-regulation of death receptor 4 (DR4) and down-regulation of Bid, surviving and cellular inhibition of apoptosis protein-2 (cIAP-2) expression. DST treatment also induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant degradation of caspase-3 substrate proteins such as poly (ADP-ribose) polymerase (PARP), phospholipase (PLC)-γ1, β-catenin and DNA fragmentation factor 45/inhibotor of caspase activated DNAse (DFF45/ICAD). Furthermore, apoptotic cell death by DST was significantly inhibited by caspase-3 specific inhibitor z-DEVD-fmk, demonstrating the important role of caspase-3. Conclusions : These findings suggest that herb prescription DST may be a potential chemotherapeutic agent for the control of human leukemia U937 cells; further study is needed to identify the active compounds.

참고문헌 (54)

  1. Loeb LA, "Multiple mutations and cancer", Proc Natl Acad Sci USA, 100(3), pp.776~781 (2003)
  2. Gilliland DG, "The molecular basis of leukemia. Hematology Am Soc Hematol Educ Program", 80~97 (2004)
  3. Abramson N, "Leukocytosis: basics of clinical assessment", Am Fam Physician, 62, pp.2053~2060 (2000)
  4. Harris P, "Human leukemic models of myelomonocytic development: a review of the HL-60 and U937cell lines", J Leukoc Biol, 37, pp.407~422 (1985)
  5. 김호철, "한약약리학", pp.294~295 (2001), 집문당
  6. 김창민, "中藥大辭典", pp.2352~2355 (1999), 鼎談
  7. 전국한의과대학 본초학교실, "본초학", pp.533~534 (1991), 영림사
  8. 辛民敎, "臨床本草學", pp.519~521 (1997), 영림사
  9. Altieri DC, "Survivin in apoptosis control and cell cycle regulation in cancer", Prog Cell Cycle Res, 5, pp.447~452 (2003)
  10. Jacotot E, "Apoptosis and cell cycle: distinct checkpoints with overlapping upstream control", Pathol Biol(Paris), 48, pp.271~279 (2000)
  11. Lundberg AS, "Control of the cell cycle and apoptosis", Eur J Cancer, 35, pp.531~539 (1999)
  12. 오천식, "영지 산자고 선학초 권백 와송이 암세포 감수성에 미치는 영향", 경희한의대논문집, 10, pp.99~115 (1987)
  13. 최정원, "C57BL", 6 암유발모델 쥐에 대한 선학초(짚신나물) 복강주사의 항암효과 탐색 및 약물대사 효소의 변화, 경원대학교 대학원, 2009
  14. 이시형, "C57BL", 6 암유발모델 쥐에 대한 선학초(짚신나물) 경구투여시 항암효과 탐색 및 약물대사 효소의 변화, 경원대학교 대학원, 2009
  15. 최순자, "선학초(짚신나물)에 의한 in vitro와 in vivo에서의 암세포사멸 기전 탐색", 박사, pp.2009
  16. 송진욱, "목향, 선학초, 하고초 추출물의 항산화 및 항암 활성", 박사, pp.2009
  17. 이선구, "蔓蔘의 과산화수소에 의한 SK-N-MC의 세포사에 미치는 영향", 동의생리병리학회지, 22(2), pp.328~332 (2008), 대한동의병리학회
  18. 전병훈, "만삼의 methanol 추출액이 mitomycin C의 세포독성효과에 미치는 영향", 한국전통의학지, 7(2), pp.5~10 (1997)
  19. 최선미, "丹蔘의 抗癌活性과 apoptosis에 미치는 影響", 동의생리병리학회지, 14(2), pp.22~47 (2000)
  20. 정국찬, "단삼(Salvia miltiorrhiza) 추출물의 암세포 증식 억제 효과에 관한 연구", 한국식품영양과학회지, 29(4), pp.726~731 (2000)
  21. 박재석, "丹蔘 추출액이 Urethane으로 유발된 생쥐의 폐암에 미치는 영향", 대한한방내과학회지, 29(3), pp.595~607 (2008), 대한한방내과학회
  22. 이경원, "Tanshinone I Suppresses the Expression of Adhesion Molecules and Metastasis of Human Breast Cancer Cells" (2008), 경상대학교 대학원
  23. prostate specific antigen pathway in LNCaP prostate cancer cells = LNCaP 전립선 암 세포에서 세포고사 유도와 androgen receptor, "Effect of tanshinone IIA on apoptosis induction and androgen receptor", pp.경희대학교 대학원, prostate specific antigen pathway에 대한 tanshinone IIA 의 효과
  24. Chung J, "Salvia miltiorrhiza inhibits tumor cell growth in association with Rb dephosphorylation through up-regulation of p21 via p53-dependent pathway", Immune network, 2(1), pp.19~24 (2002)
  25. De Murcia G, "Poly(ADP-ribose) polymerase: a molecular nick-sensor", Trends Biochem Sci, 19, pp.172~176 (1994)
  26. Muller S, "Autoantibodies reacting with poly(ADP-ribose) and with a zinc-finger functional domain of poly(ADP-ribose) polymerase involved in the recognition of damaged DNA", Clin Immunol Immunopathol, 73, pp.187~196 (1994)
  27. Los M, "The role of caspases in development, immunity, and apoptotic signal transduction: lessons from knockout mice", Immunity, 10, pp.629~639 (1999)
  28. Tewari M, "Yama", CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase, 1995, pp.81, 801~809
  29. Lazebnik YA, "Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE", Nature, 371, pp.346~347 (1994)
  30. Kaufmann SH, "Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis", Cancer Res, 53, pp.3976~3985 (1993)
  31. 류성호, "The mechanism of phospholipase C-gamma 1 regulation", EXPERIMENTAL AND MOLECULAR MEDICINE, 32(3), pp.101~109, KOREAN SOC MED BIOCHEMISTRY MOLECULAR
  32. Rhee SG, "Regulation of phosphoinositide -specific phospholipase C isozymes", J Biol Chem, 272, pp.15045~15048 (1997)
  33. Kamat A, "Phospholipase C-gamma1: regulation of enzyme function and role in growth factor-dependent signal transduction", Cytokine Growth Factor Rev, 8, pp.109~117 (1997)
  34. Nishizuka Y, "Early studies of protein kinase C: a historical perspective", Methods Mol Biol, 233, pp.9~18 (2003)
  35. Berridge MJ, "Inositol trisphosphate, a novel second messenger in cellular signal transduction", Nature, 312, pp.315~321 (1984)
  36. Myklebust JH, "Activation of phosphatidylinositol 3-kinase is important for erythropoietin-induced erythropoiesis from CD34(+) hematopoietic progenitor cells", Exp Hematol, 30, pp.990~1000 (2002)
  37. Bae SS, "Proteolytic cleavage of phospholipase C-gamma1 during apoptosis in Molt-4 cells", FASEB J, 14, pp.1083~1092 (2000)
  38. Olmeda D, "Beta-catenin regulation during the cell cycle: implications in G2", M and apoptosis, 2003, pp.14, 2844~2860
  39. Wijnhoven BP, "E- cadherin-catenin cell-cell adhesion complex and human cancer", Br J Surg, 87, pp.992~1005 (2000)
  40. Johnson JP, "Cell adhesion molecules in the development and progression of malignant melanoma", Cancer Metastasis Rev, 18, pp.345~357 (1999)
  41. Polakis P, "More than one way to skin a catenin", Cell, 105, pp.563~566 (2001)
  42. Neufeld KL, "APC-mediated downregulation of beta-catenin activity involves nuclear sequestration and nuclear export", EMBO Rep, 1, pp.519~523 (2000)
  43. Henderson BR, "Nuclear-cytoplasmic shuttling of APC regulates beta-catenin subcellular localization and turnover", Nat Cell Biol, 2, pp.653~660 (2000)
  44. Fukuda K, "Apoptosis-associated cleavage of beta -catenin in human colon cancer and rat hepatoma cells", Int J Biochem Cell Biol, 31, pp.519~529 (1999)
  45. Fukushima K, "Solution structure of the DFF-C domain of DFF45", ICAD. A structural basis for the regulation of apoptotic DNA fragmentation, 2002, pp.321, 317~327
  46. Lechardeur D, "Determinants of the nuclear localization of the heterodimeric DNA fragmentation factor(ICAD", CAD), 2000, pp.150, 321~334
  47. Widlak P, "Discovery, regulation, and action of the major apoptotic nucleases DFF40", CAD and endonuclease G, 2005, pp.94, 1078~1087
  48. Todor A, "Hypoxia-induced cleavage of caspase-3 and DFF45", ICAD in human failed cardiomyocytes, 2002, pp.283, 990~995
  49. Widlak P, "The DFF40", CAD endonuclease and its role in apoptosis, 2000, pp.47, 1037~1044
  50. Nagata S, "Apoptotic DNA fragmentation", Exp Cell Res, 256, pp.12~18 (2000)
  51. Thomas DA, "DFF45", ICAD can be directly processed by granzyme B during the induction of apoptosis, 2000, pp.12, 621~632
  52. Seon-Yong Jeong, "The role of mitochondria in apoptosis", BMB reports, 41(1), pp.11~22 (2008), 한국생화학분자생물학회
  53. Cory S, "Adams JM. The Bcl-2 family: roles in cell survival and oncogenesis", Oncogene, 22, pp.8590~8607 (2003)
  54. Bouillet P, "The role of the pro -apoptotic Bcl-2 family member bim in physiological cell death", Ann N Y Acad Sci, 926, pp.83~89 (2000)

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