(3.215.77.193) 您好!臺灣時間:2021/04/17 00:32
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:石麗珍
研究生(外文):Li-jane Shih
論文名稱:綠茶表沒食子酸酯型唲茶素酸酯對人類胎盤細胞生長調節之訊息傳遞
論文名稱(外文):Signaling of green tea epigallocatechin-3- gallate in regulating growth of human placental cells
指導教授:高永旭
指導教授(外文):Yung-Hsi Kao
學位類別:博士
校院名稱:國立中央大學
系所名稱:生命科學系
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:英文
論文頁數:110
中文關鍵詞:綠茶表沒食子酸酯型唲茶素酸酯胎盤絨毛膜癌細胞絲裂原活化蛋白激酶AMP蛋白激酶
外文關鍵詞:Green teaepigallocatechin gallateplacentachoriocarcinoma cellsmitogen-activated protein kinaseAMP-activated protein kinase
相關次數:
  • 被引用被引用:0
  • 點閱點閱:175
  • 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:1
本論文主要是探討綠茶唲茶素(GTCs),特別是(-)-表沒食子酸酯型唲茶素酸酯(英文名epigallocatechin gallate;簡稱 EGCG)對人類胎盤滋養層生長的影響。第一章研究EGCG是否對人類胎盤絨毛膜癌細胞生長具有抑制作用。我們以BeWo,JEG-3和JAR等胎盤絨毛膜癌細胞株為研究素材,結果發現EGCG抑制胎盤絨毛膜癌細胞株增生,且具有時間效應與濃度效應。綠茶唲茶素中以EGCG對於抑制細胞生長作用較其他唲茶素(EC、ECG及EGC)為明顯。研究結果顯示EGCG透過AMPK,ERK,和p38等訊息路徑調控胎盤絨毛膜癌細胞的生長,而非JNK路徑。第二章探討EGCG是否會影響正常人類絨毛膜滋養層細胞的生長。研究顯示EGCG抑制細胞生長比其他唲茶素更為明顯。處理ERK1/2,p38及AMPK的抑制劑後,受EGCG誘導細胞數減少與BrdU嵌入的實驗產生拮抗作用,分別阻斷受EGCG刺激的MEK1、p38及AMPK等蛋白質的表現。而EGCG就類似於PI3K專一性抑制劑,具有抑制AKT磷酸化、細胞數及BrdU嵌入的作用。EGCG抑制HVT細胞的增生是透過ERK,P38,AMPK和AKT的路徑。其結論是EGCG在正常與癌變的絨毛滋養細胞之間可能具有相似或不同的抗增生作用機制。此論文結果說明於大量使用或長期食用EGCG,含有EGCG成分茶飲和民間藥物,是否會影響體內正常和癌變滋養層細胞的生長,值得討論。
The overall objective of this dissertation was to investigate the effects of green tea catechins (GTCs), especially epigallocatechin-3-gallate (EGCG), on the growth of human placental trophoblasts. The first chapter was to study whether EGCG induced growth inhibition of human placental choriocarcinoma cells. Using BeWo, JEG-3, and JAR choriocarcinoma cells, we discovered that EGCG suppressed the proliferation of all three of the choriocarcinoma cells in dose-dependent and time-dependent manners. A catechin-specific effect of green tea was evident; EGCG was more effective than epicatechin (EC), epicatechin gallate (ECG), and epigallocatechin (EGC) in suppressing cell growth. We found that EGCG suppressed choriocarcinoma cell growth via the AMPK, ERK, and p38 but not JNK pathways. The second chapter was to investigate whether EGCG affects mitogenesis in human villous trophoblasts (HVT). We discovered that EGCG was more effective than other GTCs in suppressing cell growth. Also, the specific inhibitors of ERK1/2, p38, or AMPK blocked EGCG-induced decreases in both cell number and bromodeoxyuridine (BrdU) incorporation, as well as respectively blocking EGCG-stimulated activities of MEK1, p38, and AMPK proteins. Moreover, EGCG was similar to the specific inhibitor of PI3K by inhibiting AKT phosphorylation, cell number and BrdU incorporation. These data imply that EGCG inhibits the growth of HVT through the ERK, p38, AMPK and AKT pathways. We concluded that EGCG acts as an anti-proliferative agent on both normal villous trophoblasts and cancerous trophoblasts can be similar through the ERK, P38, and AMPK pathways, and different through the PI3K/AKT pathways.
Table of Contents
中文摘要 .................................................................................................... I
Abstract................................................................................................... II
Declaration............................................................................................. IV
Acknowledgments..................................................................................... V
Table of Contents................................................................................... VII
List of Figures..................................................................................... VIII
Abbreviations....................................................................................... XII
General Introduction.............................................................................. 1
Chapter One.......................................................................................... 4
Abstract....................................................................................... 5
Introduction.............................................................................. 6
Materials and Methods............................................................. 9
Results........................................................................................... 14
Discussion..................................................................................... 18
Chapter Two........................................................................................ 26
Abstract.................................................................................... 27
Introduction.............................................................................. 28
Materials and Methods........................................................... 30
Results....................................................................................... 34
Discussion................................................................................. 38
General Conclusions................................................................... 46
References........................................................................................ 48
Appendix........................................................................................... 76
References
[1] Cheung, A.N., Zhang, H.J., Xue, W.C., Siu, M.K., Pathogenesis of choriocarcinoma: clinical, genetic and stem cell perspectives. Future Oncol. 2009, 5, 217-231.
[2] Lunghi, L., Ferretti, M.E., Medici, S., Biondi, C., Vesce, F., Control of human trophoblast function. Reprod Biol Endocrinol. 2007, 5, 6.
[3] Benaitreau, D., Dieudonné, M.N., Dos Santos, E., Leneveu, M.C., et al., Antiproliferative effects of adiponectin on huamn trophoblastic cell lines JEG-3 and BeWo. Biol. Reprod. 2009, 80, 1107-1114.
[4] Li, Q., Wang, H., Ye, S., Xiao, S., et al., Induction of apoptosis and inhibition of invasion in choriocarcinoma JEG-3 cells by α-calendric acid and β-calendic acid. . Prostaglandins Leukot Essent Fatty Acids. 2013, 89, 367-376.
[5] Pospechova, K., Rozehnal, V., Stejskalova, L., Vrzal, R., et al., Expression and activity of vitamin D receptor in the human placenta and in choriocarcinoma BeWo and JEG-3 cell lines. Mol Cell Endocrinol. 2009, 299, 178-187.
[6] Wang, Y., Tang, C., Wu, M., Pan, Y., et al., Dehydroascorbic acid taken up by glucose transporters stimulates estradiol production through inhibition of JNK/c-Jun/AP1 signaling in JAR cells. Mol Hum Reprod. 2014 20(8), 799-809.
[7] Grisaru-Granovsky, S., Maoz, M.., Barzilay, O., Yin, Y.J., et al., Dickkopf-1 induced apoptosis in human placental choriocarcinoma is independent of canonical Wnt signaling. Biochem Biophys Res Commun. 2006, 350, 641-647.
[8] Caüzac, M., Czuba, D., Girard, J., Hauguel-de Mouzon, S., Transduction of leptin growth signals in placental cells is independent of JAK-STAT activation.Placenta. 2003, 24, 378-384.
[9] Rusznyak, S., Szent-Gyorgyi, A., Vitamin P: flavanols as vitamins. Nature. 1936, 138, 27.
[10] Roberts, E.A.H. The chemistry of tea fermentation. J Sci Food Agric. 1952, 3, 193-198.
[11] Liao, S., Kao, Y.H., Hiipakka, R.A., Green tea: biochemical and biological basis for health benefits. Vitam Horm. 2001, 62, 1-94.
[12] Pan, M.H., Chiou, Y.S., Wang, Y.J., Ho, C.T., Lin, J.K., Multistage carcinogenesis process as molecular targets in cancer chemoprevention. Food Funct. 2011, 2, 101-110.
[13] Yang, C.S., Wang, H., Mechanistic issues concerning cancer prevention by tea catechins. Mol Nutr Food Res. 2011, 55, 819-831.
[14] Castro, D.J., Yu, Z., Lohr, C.V., Pereira, C.B., et al., Chemoprevention of dibenzo[a,l]pyrene transplacental carcinogenesis in mice born to mothers administered green tea: primary role of caffeine. Carcinogenesis. 2008, 29, 1581-1586.
[15] Chu, K.O., Wang, C.C., Chu, C.Y., Chan, K.P., et al., Pharmacokinetic studies of green tea catechins in maternal plasma and fetuses in rats. J Pharm Sci. 2006, 95, 1372-1381.
[16] Araújo, J.R., Correia-Branco, A., Pereira, A.C., Pinho, M.J., et al., Oxidative stress induced by tert-butylhydroperoxide interferes with the placental transport of glucose: in vitro studies with BeWo cells. Eur J Pharm. 2013, 720, 218-226.
[17] Monzen, S., Kashiwakura, I., Radioprotective effects of (-)-epigallocatechin-3 -gallate on human erythrocyte/granulocyte lineages. Radiat Prot Dosimetry. 2012, 152, 224-228.
[18] Correia-Branco, A., Azevedo,C.F., Araújo JR, Guimarães JT, Faria A, Keating E, Martel F. Xanthohumol impairs glucose uptake by a human first-trimester extravillous trophoblast cell line (HTR-8/SVneo cells) and impacts the process of placentation. Mol Hum Reprod. 2015, 21, 803-815.
[19] Deng, Y.T., Lin, J.K., EGCG inhibits the invasion of highly invasive CL1-5 lung cancer cells through suppressing MMP-2 expression via JNK signaling and induces G2/M arrest. J. Agric. Food Chem. 2011, 59, 13318-13327.
[20] Huang, C.H., Tsai, S.J., Wang, Y.J., Pan, M.H., et al., EGCG inhibits protein synthesis, lipogenesis, and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cells. Mol Nutr Food Res. 2009, 53, 1156-1165.
[21] Kao, Y.H., Chang, H.H., Lee, M.J., Chen, C.L., Tea, obesity, and diabetes. Mol Nutr Food Res. 2006, 50, 188-210.
[22] Lee, J.C., Chung, L.C., Chen, Y.J., Feng, T.H., et al., Upregulation of B-cell translocation gene 2 by epigallocatechin-3-gallate via p38 and ERK signaling blocks cell proliferation in human oral squamous cell carcinoma cells. Cancer Lett. 2015, 360, 310-318.
[23] Hung, P.F., Wu, B.T., Chen, H.C., Chen, Y.H., et al., Antimitogenic effect of green tea (-)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the ERK and Cdk2 pathways. Am J Physiol Cell Physiol. 2005, 288, C1094-C1108.
[24] Ku, H.C., Liu, H.S., Hung, P.F., Chen, C.L., et al., Green tea (-)-epigallocatechin gallate inhibits IGF-I and IGF-II stimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor, but not AMP-activated protein kinase pathway. Mol Nutr Food Res. 2012, 56, 580-592.
[25] Carey, E.A., Albers, R.E., Doliboa, S.R., Hughes, M., et al., AMPK knockdown in placental trophoblast cells results in altered morphology and function. Stem Cells Dev. 2014, 23, 2921-2930.
[26] Guan, Z., Li, H.F., Guo, L.L., Yang X. Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells. Arch Gynecol Obstet. 2015, 292, 337- 342.
[27] Pearson, G., Robinson, F., Gibson, T.B., Xu, B.E., et al., Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. . Endocr Rev. 2001, 22, 153-183.
[28] Lu, H., Meng, X., Yang, C.S., Enzymology of methylation of tea catechins and inhibition of catechol-O-methyltransferase by (-)-epigallocatechin gallate. Drug Metab Dispos. 2003, 31, 572-579.
[29] Suzuki, K., Yahara, S., Hashimoto, F., Uyeda, M., Inhibitory activities of (-)-epigallocatechin-3-O-gallate against topoisomerases I and II. Biol Pharm Bull. 2001, 24, 1088-1090.
[30] Hsieh, C.F., Tsuei, Y.W., Liu, C.W., Kao, C.C., et al., Green tea epigallocatechin gallate inhibits insulin stimulation of adipocyte glucose uptake via the 67-kilodalton laminin receptor and AMP-activated protein kinase pathways. Planta Med. 2010, 76, 1694-1698.
[31] Hwang, J.T., Ha, J., Park, I.J., Lee, S.K., et al., Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway. Cancer Lett. 2007, 247, 115-121.
[32] Ku, H.C., Chang, H.H., Liu, H.C., Hsiao, C.H., et al., Green tea (-)-epigallocatechin gallate inhibits insulin stimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor pathway. Am J Physiol Cell Physiol. 2009, 297, C121-C132.
[33] Alessi, D.R., Cuenda, A., Cohen, P., Dudley, D.T., Saltiel, A.R., PD98059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J Biol Chem. 1995, 270, 27489-27494.
[34] Engelman, J.A., Lisanti, M.P., Scherer, P.E., Specific inhibitors of p38 mitogen-activated protein kinase block 3T3-L1 adipogenesis. J Biol Chem. 1998, 27, 32111-32120.
[35] Brunn, G.J., Williams, J., Sabers, C., Wiederrecht, G., et al., Direct inhibition of the signaling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002. EMBO J. 1996, 15, 5256-5267.
[36] Ku, H.C., Tsuei, Y.W., Kao, C.C., Weng, J.T., et al., Green tea (-)-epigallocatechin gallate suppresses IGF-I and IGF-II stimulation of 3T3-L1 adipocyte glucose uptake via the glucose transporter 4, but not glucose transporter 1 pathway. Gen Comp Endocrinol. 2014, 199, 46-55.
[37] Albrecht, D.S., Clubbs, E.A., Ferruzzi, M., Bomser, J.A., Epigallocatechin-3- gallate (EGCG) inhibits PC-3 prostate cancer cell proliferation via MEK-independent ERK1/2 activation. Chem Biol Interact. 2008, 171, 89-95.
[38] Vayalil, P.K., Katiyar, S.K., Treatment of epigallocatechin-3-gallate inhibits matrix metalloproteinases-2 and -9 via inhibition of activation of mitogen-activated protein kinases, c-jun and NF-kappaB in human prostate carcinoma DU-145 cells. Prostate. 2004, 59, 33-42.
[39] Siddiqui, I.A., Adhami, V.M., Afaq, F., Ahmad, N., Mukhtar, H., Modulation of phosphatidylinositol-3-kinase/protein kinase B- and mitogen-activated protein kinase-pathways by tea polyphenols in human prostate cancer cells. J Cell Biochem. 2004, 91, 232-242.
[40] Hou, Z., Lambert, J.D., Chin, K.V., Yang, C.S., Effects of tea polyphenols on signal transduction pathways related to cancer chemoprevention. Mutat Res. 2004, 555, 3-19.
[41] Kao, Y.H., Hiipakka, R.A., Liao, S., Modulation of endocrine systems and food intake by green tea epigallocatechin gallate. Endocrinology. 2000, 141, 980-987.
[42] Weng, C.J., Yen, G.C., Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Cancer Metastasis Rev. 2012, 31, 323-351.
[43] Yang, C.S., Wang, X., Lu, G., Picinich, S.C., Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nat Rev Cancer. 2009, 9, 429-439.
[44] Yang, C.S., Chen, L., Lee, M.J., Balentine, D., Kuo, M.C., Schantz, S.P., Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers. Cancer Epidemiol Biomark Prev. 1998, 7, 351-354.
[45] Chow, H.H., Hakim, I.A., Vining, D.R., Crowell, J.A., Ranger-Moore J, et al., Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of polyphenon E in healthy individuals. Clin Cancer Res. 2005, 11, 4627-4633.
[46] Chow, H.H., Cai, Y., Alberts, D.S., Hakim, I., Dorr, R., Shahi, F., et al., Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomark Prev. 2001, 10, 53-58.
[47] Unno, T., Kondo, K., Itakura, H., Takeo, T., Analysis of (-)-epigallocatechin gallate in human serum obtained after ingesting green tea. Biosci Biotechnol Biochem. 1996, 60, 2066-2068.
[48] Ullmann, U., Haller, J., Decourt, J.P., Girault, N., Girault, J., et, al. A single ascending dose study of epigallocatechin gallate in healthy volunteers. J Int Med Res. 2003, 31, 88-101.
[49] Feng, W.Y., Metabolism of green tea catechins: an overview. Curr Drug Metab. 2006, 7, 755-809.
[50] Fournier, T., Guibourdenche, J., Evain-Brion, D., Review: hCGs: different sources of production, different glycoforms and functions. Placenta. 2015, 36 Suppl, S60-S65.
[51] Tachibana, H., Koga, K., Fujimura, Y., Yamada, K., A receptor for green tea polyphenol EGCG. Nat Struct Mol Biol. 2004, 11, 380-381.
[52] van den Brûle, F.A., Price, J., Sobel, M.E., Lambotte, R., Castronovo, V., Inverse expression of two laminin binding proteins, 67LR and galectin-3, correlates with the invasive phenotype of trophoblastic tissue. Biochem Biophys Res Commun. 1994, 201, 388-393.
[53] Kumazoe, M., Sugihara K., Tsukamoto, S., Huang, Y., Tsurudome, Y., Suzuki, T., et al., 67-kDa laminin receptor increases cGMP to induce cancer-selective apoptosis, . J Clin Invest 2013, 123 787-799.
[54] Chang, J.Z., Yang, W.H., Deng, Y.T., Chen, H.M., Kuo, M.Y., EGCG blocks TGFβ1-induced CCN2 by suppressing JNK and p38 in buccal fibroblasts. Clin Oral Investig. 2013, 17, 455-461.
[55] Lee, M.H., Kwon, B.J., Koo, M.A., You, K.E., Park, J.C., Mitogenesis of vascular smooth muscle cell stimulated by platelet-derived growth factor-bb is inhibited by blocking of intracellular signaling by epigallocatechin-3-O -gallate. Oxid Med Cell Longev. 2013, 2013, 827905.
[56] Haslinger, P., Haider, S., Sonderegger, S., Otten, J.V., et al., AKT isoforms 1 and 3 regulate basal and epidermal growth factor-stimulated SGHPL-5 trophoblast cell migration in humans. Biol Reprod. 2013, 88, 54.
[57] Sonderegger, S., Haslinger, P., Sabri, A., Leisser, C., et al., Wingless (Wnt)-3A induces trophoblast migration and matrix metalloproteinase-2 secretion through canonical Wnt signaling and protein kinase B/AKT activation. Endocrinology. 2010, 151, 211-220.
[58] Petroff, M.G., Phillips, T.A., Ka, H., Pace, J.L., Hung, J.S., Isolation and culture of term human trophoblast cells. Methods Mol Med. 2006, 121, 203-217.
[59] Favata, M.F., Horiuchi, K.Y., Manos, E.J., Daulerio, A.J., et al., Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem. 1998, 273, 18623-18632.
[60] Yu, L., Zhao, Y., Fan, Y., Wang, M., Xu, S., Fu, G., Epigallocatechin-3 gallate, a green tea catechin, attenuated the downregulation of the cardiac gap junction induced by high glucose in neonatal rat cardiomyocytes. Cell Physiol Biochem. 2010, 26, 403-412.
[61] Wu J, Xu, X., Li, Y., Kou, J., et al., : Quercetin, luteolin and epigallocatechin gallate alleviate TXNIP and NLRP3-mediated inflammation and apoptosis with regulation of AMPK in endothelial cells. . Eur J Pharmacol 2014, 745, 59-68.
[62] Handwerger, S., New insights into the regulation of human cytotrophoblast cell differentiation. Mol Cell Endocrinol. 2010, 323, 94-104.
[63] Shih, L.J., Lin, Y.R., Lin, C.K., Liu, H.S., Kao, Y.H., Green tea (-)-epigallocatechin gallate induced growth inhibition of human placental choriocarcinoma cells. Placenta. 2016, 41, 1-9.
[64] Niazi, M., Coleman, D.V., Loeffler, F.E., Trophoblast sampling in eary pregnancy. Culture of rapidly dividing cells from immature placental villi. Br J Obstet Gynaecol. 1981, 88, 1081-1085.
[65] Fischer, I., Redel, S., Hofmann, S., Kuhn, C., Friese, K., Walzel, H., Jeschke, U., Stimulation of syncytium formation in vitro in human trophoblast cells by galectin-1. Placenta. 2010, 31, 825-832.
[66] Hills, F.A., Elder, M.G., Chard, T., Sullivan, M.H., Regulation of human villous trophoblast by insulin-like growth factors and insulin-like growth factor-binding protein-1. J Endocrinol. 2004, 183, 487-496.
電子全文 電子全文(網際網路公開日期:20210621)
連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
無相關期刊
 
無相關點閱論文
 
系統版面圖檔 系統版面圖檔