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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 顧記華 | |
| dc.contributor.author | Shu-yin Hsiao | en |
| dc.contributor.author | 蕭淑尹 | zh_TW |
| dc.date.accessioned | 2021-06-13T02:03:18Z | - |
| dc.date.available | 2009-08-08 | |
| dc.date.copyright | 2007-08-08 | |
| dc.date.issued | 2007 | |
| dc.date.submitted | 2007-07-05 | |
| dc.identifier.citation | 參考文獻
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Trends in Cell Biology 16, 264-272 (2006). 20. Cande, C. et al. AIF and cyclophilin A cooperate in apoptosis-associated chromatinolysis. Oncogene 23, 1514-1521 (2004). 21. Li, J.Z. & Lee, A.S. Stress induction of GRP78/BiP and its role in cancer. Current Molecular Medicine 6, 45-54 (2006). 22. Fan, T.J., Han, L.H., Cong, R.S. & Liang, J. Caspase family proteases and apoptosis. Acta Biochimica Et Biophysica Sinica 37, 719-727 (2005). 23. Erlich, S. et al. Ras inhibition results in growth arrest and death of androgen-dependent and androgen-independent prostate cancer cells. Biochemical Pharmacology 72, 427-436 (2006). 24. Oesterling, J.E. et al. Serum prostate-specific antigen in a community-based population of healthy men. Establishment of age-specific reference ranges. Jama 270, 860-4 (1993). 25. Catalona, W.J. et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 324, 1156-61 (1991). 26. Hershko, A. Mechanisms and regulation of the degradation of cyclin B. Philosophical Transactions of the Royal Society of London Series B-Biological Sciences 354, 1571-1575 (1999). 27. Daugas, E. et al. Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis. Febs Letters 476, 118-123 (2000). 28. Grubb, D.R., Ly, J.D., Vaillant, F., Johnson, K.L. & Lawen, A. Mitochondrial cytochrome c release is caspase-dependent and does not involve mitochondrial permeability transition in didemnin B-induced apoptosis. Oncogene 20, 4085-4094 (2001). 29. Gardai, S.J. et al. Phosphorylation of Bax Ser(184) by Akt regulates its activity and apoptosis in neutrophils. Journal of Biological Chemistry 279, 21085-21095 (2004). 30. Kim, B.J., Ryu, S.W. & Song, B.J. JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells. J Biol Chem 281, 21256-65 (2006). 31. Wu, Y., Zhang, H.T., Dong, Y., Park, Y.M. & Ip, C. Endoplasmic reticulum stress signal mediators are targets of selenium action. Cancer Research 65, 9073-9079 (2005). 32. Artus, C. et al. CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathwayin human erythroleukemia cells. Oncogene 25, 5741-5751 (2006). 33. Polster, B.M., Basanez, G., Etxebarria, A., Hardwick, J.M. & Nicholls, D.G. Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. Journal of Biological Chemistry 280, 6447-6454 (2005). 34. Tinhofer, I. et al. Stressful death of T-ALL tumor cells following treatment with the antitumor agent Tetrocarcin-A. Faseb Journal 16, 1295-+ (2002). 35. Lui, J.C.K. & Kong, S.K. Heat shock protein 70 inhibits the nuclear import of apoptosis-inducing factor to avoid DNA fragmentation in TF-1 cells during erythropoiesis. Febs Letters 581, 109-117 (2007). 36. Mycko, M.P. et al. Inducible heat shock protein 70 promotes myelin autoantigen presentation by the HLA class II. Journal of Immunology 172, 202-213 (2004). 37. Mi, Y. et al. Apoptosis in leukemia cells is accompanied by alterations in the levels and localization of nucleolin. J Biol Chem 278, 8572-9 (2003). 38. Srivastava, M. & Pollard, H.B. Molecular dissection of nucleolin's role in growth and cell proliferation: new insights. Faseb Journal 13, 1911-1922 (1999). 39. Finucane, D.M., Waterhouse, N.J., Amarante-Mendes, G.P., Cotter, T.G. & Green, D.R. Collapse of the inner mitochondrial transmembrane potential is not required for apoptosis of HL60 cells. Exp Cell Res 251, 166-74 (1999). 40. Leist, M., Single, B., Castoldi, A.F., Kuhnle, S. & Nicotera, P. Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med 185, 1481-6 (1997). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/30416 | - |
| dc.description.abstract | 利用sulforhodamine B (SRB) assay大規模的篩選抗癌藥物後，半合成藥物NS240062(5-[4-Acridin-9-ylamino]phenyl]-5-methyl-3-methylenedihydrofuran-2-one)在前列腺細胞癌及許多癌細胞皆展現抑制生長的效果。在荷爾蒙非依賴性前列腺癌PC-3細胞株中，NS240062抑制其生長的IC50值為0.69μg/ml。以流式細胞儀分析丟失少量染色體的亞倍體(subG1)細胞，發現凋亡細胞群的比例與時間和濃度呈現正相關。此外，使用DNA末端轉移酶介導的dUTP DNA末端標記技術(Terminal deoxynucleotidyl transferase- mediated dUTP nick-end labeling assay，TUNEL)對化合物處理過的細胞進行染色，在共軛焦螢光顯微鏡的觀察下也確實偵測到DNA斷裂的螢光亮點。使用西方墨點法進一步檢測胞內細胞凋亡相關的蛋白，結果顯示，Bcl-2家族蛋白(包括Bcl-2、Bcl-xL、Mcl-1、Bax、Bad、Bid、Bad)均沒有明顯的變化，此外，能直接參與細胞凋亡的caspase也沒有活化裂解的跡象。然而，在共軛焦顯微鏡下觀察到凋亡誘導因子(Apoptosis-inducing factor，AIF)在NS240062處理下有逐漸移進細胞核內的趨勢。此外，處理化合物6~12個小時後除了可看到凋亡誘導因子（AIF）移動，也發現核仁蛋白（nucleolin）有斷裂的現象。整體而言，NS240062引起的細胞凋亡的機轉主要是與AIF的分布、nucleolin的斷裂相關，而非經由活化caspase所造成的結果。 | zh_TW |
| dc.description.abstract | After a large scale anticancer screening by sulforhodamine B (SRB) assays, we found that a semi-synthetic compound, numbered NS240062, displayed the anti-proliferative activity in several cancer cell lines including human prostate cancer cell lines. The concentration for the 50% inhibition of cell growth (IC50) was 0.69 μg/ml in PC-3, an androgen-independent prostate cancer cell line. After the detection of cell-cycle progression by FACScan flow cytometric analysis, NS240062 induced time- and concentration-dependent increase in hypodiploid phase (apoptosis). The apoptotic cell death was confirmed by TUNEL reaction assay. The Western immunoblot assay showed that NS240062 did not induce any alteration in the expression of Bcl-2 family protein members, including Bcl-2, Bcl-xL, Mcl-1, Bax, Bad, Bid and Bad. Furthermore, it did not induce any activation of caspases. Intriguingly, NS240062 triggered a time-dependent nuclear translocation of apoptosis-inducing factor (AIF) using immunoblotting of nuclear fraction and confocal immunochemical examination. The onset of AIF translocation was six to twelve hours after the compound exposure. Moreover, the data also demonstrated the occurrence of nucleolin cleavage by NS240062. Collectively, our data suggest that NS240062 induces apoptotic cell death in PC-3 cells through AIF- and nucleolin-involved while caspase-independent pathways. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T02:03:18Z (GMT). No. of bitstreams: 1 ntu-96-R93423013-1.pdf: 4140207 bytes, checksum: 1c201b1d1a204240a00e4efa6a2896c1 (MD5) Previous issue date: 2007 | en |
| dc.description.tableofcontents | 中文摘要 Ⅰ
英文摘要 Ⅱ 目錄 Ⅲ 第一章 緒論 1 第二章 文獻回顧 4 ㄧ、細胞凋亡 4 A.粒線體引起的死亡途徑 4 B.細胞核DNA受損反應 5 C.細胞週期 6 D.凋亡誘導因子AIF 6 E.核仁蛋白nucleolin 7 F.葡萄糖調控蛋白GRP78/Bip 8 G.Caspase 8 H. Bcl-2 family 9 二、前列腺癌細胞 9 A.前列腺癌簡介 9 B.前列腺癌細胞株 10 三、酵素簡介 11 A. 酵素活性的調節 11 B. 磷酸化 11 C. 酵素的抑制方式 11 第三章 實驗材料與方法 13 ㄧ、實驗材料 13 A.細胞培養 14 B.細胞計數 14 二、實驗方法 15 A.腫瘤細胞生長測定 15 B.流式細胞儀測定細胞凋亡與細胞週期 15 C.流式細胞儀測定粒線體膜電位 16 D. 蛋白質萃取法 16 E. 蛋白質定量及西方墨點法 18 F.小RNA干擾序列 19 G.DNA末端標記法 19 H.DNA片段分析實驗 20 I. 免疫螢光染色法 21 J. 免疫沉澱法 21 K. 資料分析 22 第四章 實驗結果 23 第五章 實驗討論 28 第六章 結論 33 參考文獻 60 縮寫表 63 | |
| dc.language.iso | zh-TW | |
| dc.subject | 核仁蛋白 | zh_TW |
| dc.subject | 前列腺癌細胞 | zh_TW |
| dc.subject | 凋亡 | zh_TW |
| dc.subject | 凋亡誘導因子 | zh_TW |
| dc.subject | nucleolin | en |
| dc.subject | apoptosis | en |
| dc.subject | NS240062 | en |
| dc.subject | prostate cancer | en |
| dc.subject | AIF | en |
| dc.title | NS240062在人類前列腺癌細胞之凋亡作用研究 | zh_TW |
| dc.title | Investigation of NS240062-Mediated Apoptotic Effect in Human Prostate Cancer Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 95-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 黃聰龍,楊家榮,沈麗娟,孔繁璐 | |
| dc.subject.keyword | 前列腺癌細胞,凋亡,凋亡誘導因子,核仁蛋白, | zh_TW |
| dc.subject.keyword | NS240062,apoptosis,prostate cancer,AIF,nucleolin, | en |
| dc.relation.page | 64 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2007-07-06 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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