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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 沈湯龍 | |
| dc.contributor.author | Wen-Ling Yao | en |
| dc.contributor.author | 姚玟伶 | zh_TW |
| dc.date.accessioned | 2021-06-15T06:14:04Z | - |
| dc.date.available | 2015-08-13 | |
| dc.date.copyright | 2010-08-13 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-08-12 | |
| dc.identifier.citation | Algar, E.M., Khromykh, T., Smith, S.I., Blackburn, D.M., Bryson, G.J., and Smith, P.J.
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Biochim Biophys Acta 1500, 280-290. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/47711 | - |
| dc.description.abstract | Cordycepin (3’-deoxyadenosine) 為冬蟲夏草 (Cordyceps sinesis) 之萃取物。冬蟲夏草自古以來即為中國珍貴藥材之一，於古醫書中記載，其具有補益肺腎器官，協
定腎臟之功能，現今被認為可調節人體免疫系統，具有強身健體之效用，而其萃取物，Cordycepin 亦被認為具有抗腫瘤，抗菌之功用。然而，於先前研究之中，對於 Cordycepin 於抗癌作用上，相關的細胞及分子作用機制探討的並不多，故於此研究中，主要探討 Cordycepin 於癌細胞上所造成的抑制細胞遷移/侵入、增生、存活等現象之相關作用機制。我們發現 Cordycepin 會降低肝腫瘤細胞 (HCC)SK-Hep-1 與血癌細胞 (leukemia) U937 細胞之增生現象，並透過減少 integrin ɑ6β1及增加 E-cadherin 的表現量，進而抑制了 SK-Hep-1 細胞之遷移/侵入現象。根據研究結果顯示，Cordycepin 以調控 β-catenin 表現量之方式，影響了 U937 細胞之增生現象，而造成抗癌作用之產生；我們發現，Cordycepin 藉由降低 Akt 之磷酸化現象，進一步調節了其下游分子 Glycogen synthase kinase 3 (GSK-3) 的活性，促使了 β-atenin 進行降解作用，降低 β-catenin 進入核中的量，使得其下游分子cyclin D1 的表現量減少，最終抑制了 U937 細胞增生之現象。 Cordycepin 除了藉由調控 β-catenin 表現量之方式來控制細胞增生外，我們發現了另一轉錄因子，Wilms’tumor 1 (WT1)，可能也參與了調控細胞增生作用；Cordycepin 可抑制 WT1 的位移作用，減少 WT1 進到核中的量，進而影響促使其下游分子 c-Myc及 Bcl-2 之表現，而抑制 U937 細胞之增生。藉由此研究，可得知 Cordycepin 抑制肝腫瘤及血癌細胞生長是經由不一樣的作用機制，而 Cordycepin 也可作為一具有潛力之抗癌藥物分子。 | zh_TW |
| dc.description.abstract | Cordycepin (3’-deoxyadenosine), a well known bioactive compound extracted from a traditional Chinese medicine with complex of fungus (Cordyceps spp.) and infected caterpillar-grown, has been reported to contribute to the anti-tumor, insecticidal and anti-bacterial activity. However, the cellular and molecular effect of cordycepin to cause anti-cancer action has never been elucidated. In this study, we test the anti-migratory/invasive, anti-proliferative and anti-survival effects and evaluate the molecular targets
of cordycepin in human hepatocellular carcinoma (HCC) and human leukemia cells. We found that cordycepin significantly suppressed cell proliferation of SK-Hep-1 (a HCC cell line) and U937 (a human leukemic monocyte lymphoma) cells. Cordycepin inhibits cell migration/invasion which is correlated with decreased expression of adhesive molecules, integrin β1 and α6 with a concentration dependent manner in SK-Hep-1 cells. Furthermore, a hallmark suppressor of cancer cell epithelial-mesenchymal transition (EMT) and migration/invasion, E-cadherin, was increased by treatment of cordycepin in SK-Hep1 cells. In U937 leukemia cells, the expression of β-catenin and its downstream cell cycle regulator, cyclin D1 were decreased upon cordycepin treatment. Cordycepin reduces nuclear translocation of β-catenin and its stability through a proteasome-dependent protein degradation mechanism. Degradation of β-catenin can be restored by inhibitor of glycogen synthase kinase 3 (GSK-3) suggests the GSK-3/β-catenin plays an important role on cordycepin suppressed leukemia cell proliferation. Furthermore, cordycepin represses the level of phosphorylated Akt which is well known to be the upstream signal regulator to control GSK-3 activity. Thus, cordycepin inhibits leukemia cell growth possibly via the PI3-K/Akt/GSK-3/β-catenin signal pathway. Moreover, it has been well characterized that a transcriptional factor, Wilms Tumor 1 (WT1) plays as an essential factor to regulate leukemia cell proliferation. We have observed that cordycepin inhibits the WT1 translocation and activation. Taken together, these results suggest that cordycepin suppresses HCC and leukemia cancer progression by distinct mechanisms. Cordycepin reduces HCC migration/invasion by affecting expression of cell adhesion molecules but inhibits leukemia cell proliferation by tightly controlling signal pathway and transcriptional regulators. In conclusion, our study reveals that cordycepin may serve as a potential small molecular agent for therapeutic strategy to suppress tumor growth and metastasis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T06:14:04Z (GMT). No. of bitstreams: 1 ntu-99-R97633015-1.pdf: 23079714 bytes, checksum: e43df8e018c64029bf3d562d70b0c2c3 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | CONTENTS......................................................................................................Ⅰ
LIST of FIGURES.......................................................................................... Ⅲ 中文摘要...................................................................................................... Ⅳ ABSTRACT................................................................................................... Ⅴ INTRODUCTION............................................................................................ 1 MATERIALS and METHODS......................................................................... 11 Reagents.................................................................................................... 11 Cell culture..................................................................................................11 Western blotting analysis.............................................................................12 Cell migration assay....................................................................................12 Cell invasion assay......................................................................................13 Cell viability assay.......................................................................................13 Preparation of nuclear extraction................................................................ 13 RESULTS......................................................................................................15 Effect of cordycepin on morphological changes and cell viability in SK-Hep-1 cells.............................................................................................................15 Effect of cordycepin on cell migration and invasion in SK-Hep-1 cells........ 16 The expression profile of cell adhesion/migration molecules.......................16 Effects of cordycepin in U937 cells.............................................................. 17 The apoptotic effects of cordycepin in U937 cells.........................................18 The expression profile of cell adhesion/migration molecules in U937 cells...19 Cordycepin engaged in the degradation of β-catenin un U937 cells............ 20 Cordycepin involved in the degradation of β-catenin through GSK-3 and Akt pathway...................................................................................................... 21 Cordycepin engaged in WT1 translocation in U937 cells.............................. 22 Expression of downstream factors of WT1 in U937 cells.............................. 23 DISCUSSION................................................................................................. 24 FIGURES........................................................................................................29 REFERENCES................................................................................................. 50 | |
| dc.language.iso | en | |
| dc.subject | 細胞遷移/附著 | zh_TW |
| dc.subject | 血癌細胞 | zh_TW |
| dc.subject | 肝腫瘤細胞 | zh_TW |
| dc.subject | 細胞增生 | zh_TW |
| dc.subject | glycogen synthesis kinase 3 | en |
| dc.subject | cordycepin | en |
| dc.subject | hepatocellular carcinoma | en |
| dc.subject | leukemia | en |
| dc.subject | cell migration/adhesion | en |
| dc.subject | cell proliferation | en |
| dc.subject | integrins | en |
| dc.subject | beta-catenin | en |
| dc.title | Cordycepin 於癌細胞之細胞與分子機制之探討 | zh_TW |
| dc.title | The Cellular and Molecular Effects of Cordycepin on Cancer | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 劉俊揚,徐松錕,郭呈欽 | |
| dc.subject.keyword | 肝腫瘤細胞,血癌細胞,細胞遷移/附著,細胞增生, | zh_TW |
| dc.subject.keyword | cordycepin,hepatocellular carcinoma,leukemia,cell migration/adhesion,cell proliferation,integrins,beta-catenin,glycogen synthesis kinase 3, | en |
| dc.relation.page | 56 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-08-12 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 植物病理與微生物學研究所 | zh_TW |
| 顯示於系所單位： | 植物病理與微生物學系 | |
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