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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63626完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蔣丙煌(Been-Huang Chiang) | |
| dc.contributor.author | Ting-Yi Li | en |
| dc.contributor.author | 李亭逸 | zh_TW |
| dc.date.accessioned | 2021-06-16T17:15:06Z | - |
| dc.date.available | 2015-08-27 | |
| dc.date.copyright | 2012-08-27 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-18 | |
| dc.identifier.citation | 大腸直腸癌盛行的國家(2011)。取自：世界衛生組織http://www.who.int/en/。
台灣地區 2009年主要死因統計(2010)。取自：行政院衛生署衛生統計資訊網http://www.doh.gov.tw。 吳哲誠。2011。以Wnt/β-catenin訊息路徑探討薑中活性成份對於大腸直腸癌預防功效與機轉之研究。國立臺灣大學食品科技研究所碩士論文 林瑜珊。2007。6-shogaol 藉由氧化壓力和活化 caspases 訊息傳遞機轉誘導人類肝癌 Mahlavu 細胞株計畫性死亡的研究。輔英科技大學醫事技術系碩士論文。 謝敏琪。2007。研究薑之成分作為癌症化學預防試劑之作用機轉。國立高雄海洋科技大學水產食品科學研究所碩士論文。 徐麗芬、黃啟彰。2007。開發藥用植物資源於癌症化學預防之應用中央研究院週報 第1152期 Robert A. Weinberg. (2007). The Biology of Cancer.(pp.25-56) Garland Science. Ali, B. H.; Blunden, G.; Tanira, M. O.; Nemmar, A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem. Toxicol. 2008, 46, 409-420. Bhattarai, S.; Tran, V. H.; Duke, C. C. Stability of [6]-gingerol and [6]-shogaol in simulated gastric and intestinal fluids. J. Pharm. Biomed. Anal. 2007, 45, 648-653. Brewer, C.; N. Yeager ; Di Cristofano, A. Thyroid-Stimulating Hormone–Initiated Proliferative Signals Converge In vivo on the mTOR Kinase without Activating AKT. Can. res. 2007, 67,8002-6. Chen, C. Y.; Liu, T. Z.; Liu, Y. W.; Tseng, W. C.; Liu, R. H.; Lu, F. J.; Lin, Y. S.; Kuo, S. H.; Chen, C. H. 6-shogaol (alkanone from ginger) induces apoptotic cell death of human hepatoma p53 mutant Mahlavu subline via an oxidative stress-mediated caspase-dependent mechanism. J. Agric. Food Chem. 2007, 55, 948−954. Chen, Y.; Azad M. B.; Gibson, S.B. Methods for detecting autophagy and determining autophagy-induced cell death. Can. J. Physiol. Pharm. 2010, 88, 285-295. Deshmukh, A. S.; Treebak, J. T. ; Long, Y.C.; Viollet, B.; Wojtaszewski, J.F.P.; Zierath, J.R. Role of adenosine 5′-monophosphate-activated protein kinase subunits in skeletal muscle mammalian target of rapamycin signaling.Mol. Endocrinol. 2008, 22, 1105-1112. Edinger, A. L. ; C. B. Thompson.Death by design: apoptosis, necrosis and autophagy. Curr. Opin. Cell Biol. 2004, 16, 663-669. Engelman, J. A. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer. 2009, 9, 550-562. Gan,F.F.; Nagle A. A.;Ang X.;Ho O. H.;Tan S.H. ;Yang H. ; Wai-Keung Chui;Chew E.H.Shogaols at proapoptotic concentrations induce G2/M arrest and aberrant mitotic cell death associated with tubulin aggregation.Apoptosis. 2011,16, 856–867 Green, D.R., Kroemer, G., The pathophysiology of mitochondrial cell death. Science. 2004, 305, 626–629. Gagne, P.; Akalu, A.; Brooks, P. C. Challenges facing antiangiogenic therapy for cancer: impact of the tumor extracellular environment. Expert Rev. Anticancer Ther. 2004, 4, 129-140. Gozuacik, D. ; Kimchi, A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene . 2004, 23, 2891-2906. Herold, M.J., McPherson, K.G., Reichardt, H.M. Glucocorticoids in T cell apoptosis and function. Cell. Mol. Life Sci. 2006, 63, 60–72. Hung, J. Y.; Hsu, Y. L.; Li, C. T.; Ko, Y. C.; Ni, W. C. Huang, M. S. Kuo, P. L. 6-Shogaol, an active constituent of dietary ginger, induces autophagy by inhibiting the AKT/mTOR pathway in human non-small cell lung cancer A549 cells. J. Agric. Food Chem. 2009, 57, 9809–9816. Jiang, B. H. ; Liu, L. Z. Role of mTOR in anticancer drug resistance: perspectives for improved drug treatment. Drug resist. update. 2008, 11, 63-76. Johansen, T. ; Lamark, T. Selective autophagy mediated by autophagic adapter proteins. Autophagy. 2011, 7, 279. Kanzawa,T.;Kondo,Y.;Ito,H.;Kondo,S.;Germano,I.Induction of Autophagic Cell Death in Malignant Glioma Cells by Arsenic Trioxide.Can. Res.2003, 63, 2103–2108 Kaminskyy, V.; Abdi,A. ; Zhivotovsky, B. A quantitative assay for the monitoring of autophagosome accumulation in different phases of the cell cycle. Autophagy.2011, 7, 83-90. Knecht, E., C.; Aguado, C.; Carcel, J.; Esteban, I.; Esteve, J.M.; Ghislat, G.; Moruno, J.F.; Vidal, J.M.; Saez, R. Intracellular protein degradation in mammalian cells: recent developments. Cell. Mol. Life Sci. 2009, 66, 2427-2443. Kourtis, N. ; Tavernarakis, N. Autophagy and cell death in model organisms.Cell Death Differ. 2008, 16, 21-30. Kroemer, G.; Galluzzi, L. ; Brenner, C. Mitochondrial membrane permeabilization in cell death. Physiol. rev. 2007, 87, 99-163. Larsen, A. K.; Escargueil,A. E. ; Skladanowski, A. Catalytic topoisomerase II inhibitors in cancer therapy. Pharmacol. therapeut. 2003, 99, 167-181. Lee, S. W.;Lim,J.H.;Kim,M. S.;Jeong.J.H.;Song,G.Y.;Lee,W. S.;Rho,M.C.Phenolic compounds isolated from Zingiber officinale roots inhibit cell adhesion.Food chem.2011,128,778-782. Lee, S.-H.; Cekanova, M.; Baek, S. J. Multiple mechanisms are involved in 6-gingerol- induced cell growth arrest and apoptosis in human colorectal cancer cells. Mol. Carcinog. 2008, 47, 197-208. Ling, H.; Yang, H.; Tan, S.H. ; Chui, W.K.; Chew, E.H. 6-Shogaol,inhibits breast cancer cellinvasion by reducing matrix metalloproteinase-9 expression via blockade ofnuclear factor-kB activation. Br J Pharmacol. 2010, 161,1763–1777. Longo, D. L.; Kasper,D. L.; Jameson, J.L.; Fauci, A.S.; Hauser, S.L.; Loscalzo, J. Cancer Is a Genetic Disease, McGraw-Hill. 2012, 83. Maiuri, M. C.; Zalckvar, E.; Kimchi, A.; Kroemer, G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Bio. 2007, 8, 741-752. Okada, H. ; Mak, T. W. Pathways of apoptotic and non-apoptotic death in tumour cells. Nat. Rev. Can.2004, 4, 592-603. Pandya, N.; Dhalla, N.; Santani, D. Angiogenesis—a new target for future therapy. Vascular Pharmacology. 2006, 44, 265-274. Pan, M.-H.; Hsieh, M.-C.; Kuo, J.-M.; Lai, C.-S.; Wu, H.; Sang, S.; Ho, C.T.6-Shogaol induces apoptosis in human colorectal carcinoma cells via ROS production, caspase activation, and GADD 153 expression. Mol. Nutr. Food Res. 2008, 52, 527-537. Schmitt, C. A. Senescence, apoptosis and therapy—cutting the lifelines of cancer. Nat. Rev. Can. 2003, 3, 286-295. Schwartz, G. K. ; Shah, M. A. . Targeting the cell cycle: a new approach to cancer therapy. J. Clin. Oncol. 2005, 23, 9408-9421. Shieh, P.C.; Chen, Y.O.; Kuo, D.H.; Chen, F.A.; Tsai, M.L.; Chang, I.S.; Wu, H., Sang, S.; Ho, C.T.; Pan, M.H. Induction of apoptosis by [8]-shogaol via reactive oxygen species generation, glutathione depletion, and caspase activation in human leukemia cells. J. Agric. Food Chem.2010, 58, 3847-54. Tjendraputra E.; Van H. Tran; Damien Liu-Brennan; Basil D. Roufogalis;Colin C. Duke.Effect of Ginger Constituents and Synthetic Analogues on Cyclo- oxygenase-2 Enzyme in Intact Cells.Biorgan.Chem ,2001, 29, 156–163. Thorburn, A. Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis, 2008, 13, 1–9. Vakifahmetoglu, H.; Olsson, M.; Zhivotovsky, B. Death through a tragedy: mitotic catastrophe. Cell Death Differ. 2008, 15, 1153-1162. Villa, P.; Kaufmann, S. H.; Earnshaw, W.C. Caspases and caspase inhibitors.Trends Biochem. Sci. 1997, 22, 388-393. Vitale, I.; Galluzzi, L.; Castedo, M.; Kroemer, G. Mitotic catastrophe: a mechanism for avoiding genomic instability.Nat. Rev. Mol. Cell Bio. 2011, 12, 385-392. Vogelstein, B.; Kinzler, K. W. Cancer genes and the pathways they control. Nat. med. 2004, 10, 789-799. Welchman, R. L.; Gordon, C. ; Mayer, R.J. Ubiquitin and ubiquitin-like proteins as multifunctional signals. Nat. Rev. Mol. Cell Bio. 2005, 6, 599-609. Wu, Y.T.; Tan, H.L.; Shui, G.; Bauvy, C.; Huang, Q.; Wenk, M.R.; Ong, C.N.; Codogno, P.; Shen, H.M. Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase.J. BioChem. 2010, 285, 10850-61. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63626 | - |
| dc.description.abstract | 自噬性細胞死亡（Autophagic cell death, Ⅱ型細胞程序性死亡）和細胞凋亡（Apoptosis , I型細胞程序性死亡）是細胞死亡的兩種不同形式。他們皆為細胞反應外界的壓力所產生的變化，在某些狀況下，自噬(Autophagy)為構成細胞對外在環境的適應，但在癌症抑制上，其又構成了另一種細胞死亡途徑的關係。薑(Ginger)是亞洲國家使用已久天然食品與藥草，在薑萃取物中，薑酮醇(Gingerol)、薑烯酚(Shogaol)是主要的活性成分，其中6-shogaol具有良好之抗發炎活性、抗細菌和抗肝毒性，此外，6-shogaol能誘導肝癌細胞透過Akt-PI3K路徑促使其產生自噬、也被證明能誘導人類大腸癌細胞之凋亡。但有關6-shogaol對人類大腸直腸癌細胞HT-29的凋亡和自噬間之研究仍相當有限，因此，本研究以HT-29大腸直腸癌細胞模式探討6-shogaol對兩者死亡形式的關係。過去，本實驗室的研究已經證實，6-shogaol透過調節粒線體膜電位下降，可有效誘導HT-29凋亡。但對於6-shogaol的和caspase活性，凋亡和自噬性細胞死亡之間的發展尚不清楚。故我們假設6-shogaol抑制HT-29的細胞生長是通過自噬與凋亡。藉由檢測自噬相關的每一個階段的發展模式來討論其關係性。結果顯示，在存活率試驗中，6-shogaol在24小時內不呈現劑量效應，接著以流式細胞儀分析autophagososome和 autolysosome的活性、細胞膜外翻(Annexin-V)、caspase3/7的表現與DNA片斷化的情況，並以共軛焦顯微鏡證明autophagososome的形成，發現自噬和凋亡的發生原來是決定於不同的劑量與時間點，以18小時為分界，是兩者細胞死亡型式的交接點且並行不悖，並在低濃度（20 μM）下可以維持較長的自噬效應，高濃度下（80 μM）自噬性死亡和細胞凋亡皆大量表現。此外，6-shogaol對於細胞週期G2/M有阻滯的作用，可推測6-shogaol藉由G2/M阻滯、影響細胞的有絲分裂而促進細胞死亡。 | zh_TW |
| dc.description.abstract | Autophagic cell death (Type II programmed cell death) and apoptosis (Type I programmed cell death) are two distinct forms of cell death. They have a complex functional relationship in the sense that, autophagy constitutes a stress adaptation that avoids cell death (and suppresses apoptosis) and an alternative cell-death pathway. Ginger, have several phenolic alkanones among which 6-shogaol is shown to exert anti-inflammatory, anti-bacterial and anti-hepatotoxic properties. Also it has been shown to induce apoptosis in human colorectal carcinoma cells. In our previous studies, we found that 6-shogaol can induce apoptosis of HT-29 (human colorectal carcinoma cells) via modulation of mitochondrial functions. In this study, we assumed that the cell growth inhibition activity of 6-shogaol on the HT-29 is via both autophagy and apoptosis. The results showed that in the survival test, within 24 hrs treatment, effect of 6-shogaol on cell survival rate was not dose dependent. Then we used flow cytometry to analyze the autophagososome and auto- lysosome activity and did a series of apoptosis test, including Annexin-V, caspase3 / 7 activation, DNA fragment. Also, the confocal microscopy showed the formation of autophagososome which proved that the occurrence of autophagy and apoptosis was originally determined by the different doses and time points. That is, both cell death types go hand in hand and can be divided at 18 h. Autophagy can be maintained a bit longer in the low concentration (20 μM), but at high concentration (80 μM), both of autophagic death and apoptosis play significant roles. In addition, 6-shogaol which induces the G2 / M cell cycle arrest, it can be speculated that 6-shogaol affect cell mitosis and promote cell death. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T17:15:06Z (GMT). No. of bitstreams: 1 ntu-101-R99641019-1.pdf: 10931441 bytes, checksum: 15bb5692f587624c1e01aaf83a3c8993 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 第一章 文獻整理 …………………………………………………………………1
第一節 腫瘤的發生……………………………………………………………1 第二節 細胞的生長與死亡對腫瘤的調控……………………………………7 1. 細胞死亡(Cell death)…………………………………………………8 2. 細胞自噬(Autophagy) 與細胞凋亡( Apoptosis) ………………12 3. 細胞自噬與細胞凋亡是相互調節和拮抗的角色………………18 第三節 細胞自噬與細胞凋亡對腫瘤抑制的機轉………………………19 1. 細胞自噬與細胞凋亡的差別………………………………19 2. 細胞凋亡在癌症中的角色 ………………………………………19 3. 細胞自噬在癌症中的角色 ………………………………………20 4. BCL2基因家族在細胞自噬與細胞凋亡調控的角色 ……………21 第四節 大腸癌 ………………………………………………………………23 第五節 薑 (Ginger) 活性成份6-shogaol之生理活性 ……………………25 1. 薑（Ginger）的生理活性…………………………………………25 2. Shogaol抗腫瘤活性 ………………………………………………26 第六節 薑(Ginger)活性成份6-shogaol對大腸癌細胞之影響 ……………28 1. 促進ROS生成……………………………………………………28 2. 抑制發炎反應………………………………………………………28 第二章 研究目的…………………………………………………………………29 第一節 研究目的………………………………………………………29 第二節 實驗架構………………………………………………………30 第三章 實驗材料與方法…………………………………………………………31 第一節 實驗材料 …………………………………………………………… 31 1. 細胞株來源…………………………………………………………31 2. 藥品試劑……………………………………………………………31 3. 儀器與廠牌…………………………………………………………32 第二節 實驗方法………………………………………………………………33 1. 樣品配置……………………………………………………………33 2. 細胞培養……………………………………………………………33 3. 細胞存活率…………………………………………………………33 4. 細胞週期……………………………………………………………34 5. 免疫螢光染色………………………………………………………36 6. 以流式細胞儀檢測細胞自噬起始因子PI3K-mTOR表現量 ……38 7. LC3-B+PI雙染細胞檢測不同細胞週期下的Autophagic cell …40 8. 以Acridine Orange染色檢測Autolysosome ……………………42 9. 偵測磷脂醯絲胺酸外翻 (Annexin V-FITC) ……………………43 10. 以流式細胞儀觀察凋亡中期caspase3/7的表現…………………45 11. 以流式細胞儀觀察凋亡晚期TUNEL的表現……………………46 第四章 結果與討論………………………………………………………………49 第一節 6-shogaol對人類大腸直腸癌細胞株 (HT-29) 存活率之影響 ……50 第二節 以凋亡和自噬的抑制劑配合6-shogaol對大腸直腸癌細胞株 (HT-29) 存活率之影響 ……………………………………………………56 第三節 薑中活性成分6-shogaol對人類大腸直腸癌細胞株(HT-29)型態之影響 …………………………………………………………………58 第四節 以流式細胞儀觀察不同時間點細胞週期的表現 …………………61 第五節 以共軛焦顯微鏡觀察自噬體的表現 ………………………………69 第六節 以流式細胞儀定量6小時~18小時PI3K-mTOR表現量 ……………76 第七節 以流式細胞儀定量不同時間點autophagic cell 的含量 ……………82 第八節 以流式細胞儀觀察不同時間點autolysosome的表現 ………………88 第九節 以流式細胞儀觀察凋亡早期Annexin–V的表現 …………………89 第十節 以流式細胞儀觀察凋亡中期caspase3/7的表現 ……………………93 第十一節 以流式細胞儀觀察凋亡晚期TUNEL的表現 ………………………96 第五章 結論 ………………………………………………………………………99 1. 6-shogaol對Apoptosis 和Autophagy的影響……………………………99 第六章 參考文獻…………………………………………………………………102 | |
| dc.language.iso | zh-TW | |
| dc.subject | 大腸癌 | zh_TW |
| dc.subject | HT-29 | zh_TW |
| dc.subject | 6-shogaol | zh_TW |
| dc.subject | 細胞自噬 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | Apoptosis | en |
| dc.subject | HT-29 | en |
| dc.subject | 6-shogaol | en |
| dc.subject | Autophagy | en |
| dc.subject | Colonrectal cancer | en |
| dc.title | 薑中活性成份6-Shogaol對於大腸直腸癌細胞HT-29凋亡與自噬之探討 | zh_TW |
| dc.title | 6-Shogaol Induces Autophagy and Apoptosis in Human colon adenocarcinoma HT-29 Cells | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 何其儻(Chi-Tang Ho),吳明賢(Ming-Shiang Wu),鐘景光(Jing-Gung Chung) | |
| dc.subject.keyword | 大腸癌,HT-29,6-shogaol,細胞自噬,細胞凋亡, | zh_TW |
| dc.subject.keyword | Colonrectal cancer,HT-29,6-shogaol,Autophagy,Apoptosis, | en |
| dc.relation.page | 107 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-08-20 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 食品科技研究所 | zh_TW |
| 顯示於系所單位： | 食品科技研究所 | |
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