(3.236.222.124) 您好!臺灣時間:2021/05/13 02:46
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:簡毓芬
研究生(外文):Yu-Fen
論文名稱:單寧酸誘發急性骨髓性白血病癌細胞凋亡之相關研究
論文名稱(外文):Study of apoptotic effects of tannic acid in acute myeloid leukemia (HL-60)
指導教授:周芬碧周芬碧引用關係
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:生化暨生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:75
相關次數:
  • 被引用被引用:0
  • 點閱點閱:126
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
單寧酸(tannic acid)是由多個沒食子酸(gallic acid)聚合而成的糖苷體化合物,且已被證實具有抑制細菌、抑制酵素活性及止血收斂的作用(Choi O,et al , 2007)。茶葉、蕁蔴類植物、莓果及橡木中含有大量的單寧酸。在本研究中,我們發現急性骨髓性白血病(acute myeloid leukemia, AML)細胞株 HL-60在加入單寧酸的處理下,會造成細胞存活率(cell viability)的明顯下降,且下降趨勢具有濃度及時間關係。而在流式細胞儀(Flow cytometry)的分析中,發現sub-G1的細胞群會隨單寧酸的濃度提高而增多,顯示單寧酸具有誘導HL-60細胞凋亡(apoptosis)的效果。進一步以DAPI stain以及DNA電泳的分析,證實單寧酸會造成HL-60細胞染色質(chromosome)濃聚以及DNA斷裂的現象。而在分子機制的探討中發現,單寧酸所誘導的HL-60細胞凋亡,主要是透過破壞粒腺體膜電位(mitochondrial membrane potential)進而釋放出cytochrome C,並且活化caspase 8、 caspase 9 以及caspase 3,而造成poly (ADP-ribose) polymerase (PARP)的切割。此外,我們發現單寧酸對於臨床上的AML用藥(Arsenic trioxide)具有相當不錯的輔助效果。綜合以上結果,單寧酸可以有效的抑制AML細胞(HL-60)的生長,或許有助於AML的治療。

Tannic acid (TA), a glucoside of gallic acid polymer, has been shown to possess anti-bacterial, anti-enzymatic and astringent properties. Tannic acid is present in most plants and richly in tea, nettle, berries, and Oak wood. In the present study, we reported that tannic acid treatment decreased the viability of acute myeloid leukemia (AML) HL-60 cells in a dose- and time-dependent manner. Flow cytometry analysis revealed that tannic acid significantly induced apoptosis of HL-60 cells as confirmed by a dose-dependent increase of sub-G1 fraction. The further analysis of DAPI stain and DNA integrity also evidenced that tannic acid caused chromosome condensation and DNA fragmentation. The molecular analysis showed that tannic acid-induced apoptosis of HL-60 cells was associated with disruption of mitochondrial membrane potential, release of cytochrome C, activation of caspase 9 and caspase 3, and cleavage of poly (ADP-ribose) polymerase (PARP). Moreover, we demonstrated the improvement effect of tannic acid with anti-leukemia drug, Arsenic trioxide, on HL-60 cells. In conclusion, tannic acid perturbs the growth of acute myeloid leukemia cells (HL-60), suggesting it may hold potential for treatment of acute myeloid leukemia.

壹、摘要…………………………………………………………………3
貳、縮寫表………………………………………………………………5
參、緒論…………………………………………………………………7
一、白血病(Leukemia)……………………………………………7
二、急性骨隨性白血病(Acute myeloid leukemia;AML) ………… 17
三、細胞週期…………………………………………………………19
四、細胞凋亡之簡介…………………………………………………21
五、化學預防 (chemoprevention) …………………………………25
六、單寧酸(Tannic acid) ……………………………………………29
肆、研究動機……………………………………………………………31
伍、實驗材料與方法……………………………………………………33
陸、實驗結果……………………………………………………………45
柒、討論…………………………………………………………………50
捌、參考文獻……………………………………………………………55
玖、圖表與圖表說明……………………………………………………62
拾、附圖…………………………………………………………………72


張亭棟,李元善。(1984) 癌靈1號治療急性粒細胞白血病臨床分析及實驗研究。中西醫結合雜誌, 4; 19-20.
Agarwal C, Veluri R, Kaur M, Chou SC, Thompson JA, Agarwal R. (2007) Fractionation of high molecular weight tannins in grape seed extract and identification of procyanidin B2-3,3''-di-O-gallate as a major active constituent causing growth inhibition and apoptotic death of DU145 human prostate carcinoma cells. Carcinogenesis, 28; 1478-1484.
Albini A, Noonan DM, Ferrari N. (2007) Molecular pathways for cancer angioprevention. Clin Cancer Res, 13; 4320-4325.
Balduf M, Steinkraus V, Mensing H. (1994) Acute myeloid leukemia: ecchymoses as sole clinical symptom. Cutis, 53; 131-133.
Brenner C, Kroemer G. (2000) Apoptosis. Mitochondria--the death signal integrators. Science, 289; 1150-1151.
Brown G, Hughes PJ, Michell RH. (2003) Cell differentiation and proliferation--simultaneous but independent? Exp Cell Res, 291; 282-288.
Chai J, Du C, Wu JW, Kyin S, Wang X, Shi Y. (2000) Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature, 406; 855-862.
Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES, Shi Y. (2001) Structural basis of caspase-7 inhibition by XIAP. Cell, 104; 769-780.
Chen GQ, Shen ZX, Wu F, Han JY, Miao JM, Zhong HJ, Li XS, Zhao JQ, Zhu J, Fang ZW, Chen SJ, Chen Z, Wang ZY. (1996) Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Leukemia, 10; 825-828.
Chen GQ, Shen ZX, Wu F, Han JY, Miao JM, Zhong HJ, Li XS, Zhao JQ, Zhu J, Fang ZW, Chen SJ, Chen Z, Wang ZY. (1996) Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Leukemia, 10; 825-828.
Chen GQ, Shi XG, Tang W, Xiong SM, Zhu J, Cai X, Han ZG, Ni JH, Shi GY, Jia PM, Liu MM, He KL, Niu C, Ma J, Zhang P, Zhang TD, Paul P, Naoe T, Kitamura K, Miller W, Waxman S, Wang ZY, de The H, Chen SJ, Chen Z. (1997) Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood, 89; 3345-3353.
Chen YC, Shen SC, Chen LG, Lee TJ, Yang LL. (2001) Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors and lipopolysaccharide. Biochem Pharmacol, 61; 1417-1427.
Choi O, Yahiro K, Morinaga N, Miyazaki M, Noda M. (2007) Inhibitory effects of various plant polyphenols on the toxicity of Staphylococcal alpha-toxin. Microb Pathog, 42; 215-224.
Chung KT, Wong TY, Wei CI, Huang YW, Lin Y. (1998) Tannins and human health: a review. Crit Rev Food Sci Nutr, 38; 421-464.
Dbaibo GS, Kfoury Y, Darwiche N, Panjarian S, Kozhaya L, Nasr R, Abdallah M, Hermine O, El-Sabban M, de The H, Bazarbachi A. (2007) Arsenic trioxide induces accumulation of cytotoxic levels of ceramide in acute promyelocytic leukemia and adult T-cell leukemia/lymphoma cells through de novo ceramide synthesis and inhibition of glucosylceramide synthase activity. Haematologica, 92; 753-762.
Dilda PJ, Hogg PJ. (2007) Arsenical-based cancer drugs. Cancer Treat Rev, [Epub ahead of print]
Dixit R, Gold B. (1986) Inhibition of N-methyl-N-nitrosourea-induced mutagenicity and DNA methylation by ellagic acid. Proc Natl Acad Sci U S A, 83; 8039-8043.
Drexler HG, Quentmeier H, MacLeod RA, Uphoff CC, Hu ZB. (1995) Leukemia cell lines: in vitro models for the study of acute promyelocytic leukemia. Leuk Res, 19; 681-691.
Filges I, Zaman K, Michielin O, Vulliemoz D, Perey L, Stupp R. (2005) [Present chemoprevention and future vision]. Rev Med Suisse, 1; 1343-1346, 1349.
Green DR, Kroemer G. (2004) The pathophysiology of mitochondrial cell death. Science, 305; 626-629.
Gross N, Balmas K, Beretta Brognara C, Tschopp J. (2001) Expression of Fas (APO-1/CD95) and Fas ligand (FasL) in human neuroblastoma. Med Pediatr Oncol, 36; 111-114.
Harris RE, Beebe-Donk J, Alshafie GA. (2007) Cancer chemoprevention by cyclooxygenase 2 (COX-2) blockade: results of case control studies. Subcell Biochem, 42; 193-212.
Haslam E. (1996) Natural polyphenols (vegetable tannins) as drugs: possible modes of action. J Nat Prod, 59; 205-215.
Horn RC, Vargas VM. (2003) Antimutagenic activity of extracts of natural substances in the Salmonella/microsome assay. Mutagenesis, 18; 113-118.
Kerr JF, Wyllie AH, Currie AR. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer, 26; 239-257.
Kim JA. (2003) Targeted therapies for the treatment of cancer. Am J Surg, 186; 264-268.
Kischkel FC, Hellbardt S, Behrmann I, Germer M, Pawlita M, Krammer PH, Peter ME. (1995) Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form a death-inducing signaling complex (DISC) with the receptor. Embo J, 14; 5579-5588.
Lu L, Liu D, Ma X, Beklemishev A, Seiter K, Ahmed T, Chiao JW. (2006) The phenylhexyl isothiocyanate induces apoptosis and inhibits leukemia cell growth in vivo. Oncol Rep, 16; 1363-1367.
Muzio M, Chinnaiyan AM, Kischkel FC, O''Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM. (1996) FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex. Cell, 85; 817-827.
Petros AM, Olejniczak ET, Fesik SW. (2004) Structural biology of the Bcl-2 family of proteins. Biochim Biophys Acta, 1644; 83-94.
Ryan KM, Birnie GD. (1996) Myc oncogenes: the enigmatic family. Biochem J, 314 ( Pt 3); 713-721.
Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem, 73; 39-85.
Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, Chen Y, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, Wang ZY. (1997) Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood, 89; 3354-3360.
Sprick MR, Walczak H. (2004) The interplay between the Bcl-2 family and death receptor-mediated apoptosis. Biochim Biophys Acta, 1644; 125-132.
Takahashi T, Tanaka M, Brannan CI, Jenkins NA, Copeland NG, Suda T, Nagata S. (1994) Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell, 76; 969-976.
Vardiman JW, Harris NL, Brunning RD. (2002) The World Health Organization (WHO) classification of the myeloid neoplasms. Blood, 100; 2292-2302.
Wang ZY, Chen Z. (2000) Differentiation and apoptosis induction therapy in acute promyelocytic leukaemia. Lancet Oncol, 1; 101-106.
Warrell RP, Jr., de The H, Wang ZY, Degos L. (1993) Acute promyelocytic leukemia. N Engl J Med, 329; 177-189.
Wu LT, Chu CC, Chung JG, Chen CH, Hsu LS, Liu JK, Chen SC. (2004) Effects of tannic acid and its related compounds on food mutagens or hydrogen peroxide-induced DNA strands breaks in human lymphocytes. Mutat Res, 556; 75-82.
Yedjou CG, Moore P, Tchounwou PB. (2006) Dose- and time-dependent response of human leukemia (HL-60) cells to arsenic trioxide treatment. Int J Environ Res Public Health, 3; 136-140.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
1. 44. 董小萍,林俐玲,萬鑫森,1999,「台灣土壤改良原理與方法之研究」,中華水土保持學報,第30卷,第3期,第195-203頁。
2. 51. 鍾敏娟,萬鑫森,1991,「玄武岩石粉改良土壤之效應」,中國農業化學會誌,第29卷,第2期,第220-225頁。
3. 43. 萬鑫森,黃俊銘,1992,「熱帶土壤改良原理與方法之研究」,水土保持學報,第24卷,第2期,第1-9頁。
4. 17. 李咸亨(1996):台北市區工程地質分區,地工技術,第54期,四月,pp.25~34。
5. 40. 楊貫一,1991,「爐石資源化-水淬高爐爐石之反應性與研磨」,技術與訓練,第16卷,第5期,第35-44頁。
6. 35. 黃俊銘,萬鑫森,1987,「爐渣與飛灰對土壤穩定性之效應」,中華水土保持學報,第18卷,第2期,第77-82頁。
7. 34. 黃俊銘,萬鑫森,1987,「爐渣與飛灰對土壤表面電荷量之效應」,中國農業化學會誌,第25卷,第4期,第422-431頁。
8. 31. 陳慶雄,謝豪榮,1986,「穩定藥劑處理對紅土與青灰泥岩邊坡穩定效果之研究」,中華水土保持學報,第17卷,第2期,第162-182頁。
9. 22. 張菊香,萬鑫森,1993,「矽質玄武岩石粉改良土壤之效應」,中國農業化學會誌,第31卷,第2期,第247-253頁。
10. 15. 林紫慧,陳啟烈,洪崑煌,1999,「臺灣酸性土壤酸度強度特性之研究(一)測定法比較」,土壤與環境,第2卷,第3期,第265-280頁。
11. 11. 林俐玲,1996,「矽質玄武岩石粉控制土壤沖蝕功效之研究」,中華水土保持學報,第27卷,第2期,第167-174頁。
12. 7. 江慶陞,1981,「爐石的資源化」,技術與訓練,第6卷,第9期,第37-49頁。
13. 20. 朱旭(1997):捷運規劃、設計、施工面面觀,地工技術,第60期,四月,pp.4~31。
 
系統版面圖檔 系統版面圖檔