Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/12957
標題: 探討天然飲食中生物活性成分對離體中誘導細胞 凋亡與活體中抗腫瘤的研究
Investigations for induction of apoptosis in vitro and antitumor activity in vivo of the bioactive components in natural diatry
作者: 陳念谷
Chen, Nian-Gu
關鍵字: AITC;烯丙基異硫氰酸酯;GBM 8401;EGCG;TSGH-8301;HSP27;人類腦惡性膠質瘤;表沒食子兒茶素;沒食子酸酯;台灣特定人類膀胱癌;熱休克蛋白27
出版社: 獸醫學系暨研究所
引用: 第一部分 Batista LF, Kaina B, Meneghini R, Menck CF. How DNA lesions are turned into powerful killing structures: insights from UV-induced apoptosis. Mutat Res. 2009 Mar-Jun;681(2-3):197-208. Bhattacharya A, Tang L, Li Y, Geng F, Paonessa JD, Chen SC, Wong MK, Zhang Y. Inhibition of bladder cancer development by allyl isothiocyanate. Carcinogenesis. 2010 Feb;31(2):281-6. Buckner JC. Factors influencing survival in high-grade gliomas. Semin Oncol. 2003 Dec;30(6 Suppl 19):10-4. Cai J, Wang M, Li B, Wang C, Chen Y, Zuo Z. Apoptotic and necrotic action mechanisms of trimethyltin in human hepatoma G2 (HepG2) cells. Chem Res Toxicol. 2009 Sep;22(9):1582-7. Chung JG, Yang JS, Huang LJ, Lee FY, Teng CM, Tsai SC, Lin KL, Wang SF, Kuo SC. Proteomic approach to studying the cytotoxicity of YC-1 on U937 leukemia cells and antileukemia activity in orthotopic model of leukemia mice. Proteomics. 2007 Sep;7(18):3305-17. Clark GB, Thompson G, Jr., Roux SJ. Signal transduction mechanisms in plants: an overview. Curr Sci. 2001 Jan 25;80(2):170-7. Debatin KM, Krammer PH. Death receptors in chemotherapy and cancer. Oncogene. 2004 Apr 12;23(16):2950-66. Deorah S, Lynch CF, Sibenaller ZA, Ryken TC. Trends in brain cancer incidence and survival in the United States: Surveillance, Epidemiology, and End Results Program, 1973 to 2001. Neurosurg Focus. 2006 20(4):E1. Fahey JW, Zalcmann AT, Talalay P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry. 2001 Jan;56(1):5-51. Fulda S, Debatin KM. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 2006 Aug 7;25(34):4798-811. Hasegawa T, Nishino H, Iwashima A. Isothiocyanates inhibit cell cycle progression of HeLa cells at G2/M phase. Anticancer Drugs. 1993 Apr;4(2):273-9. Hayes JD, Kelleher MO, Eggleston IM. The cancer chemopreventive actions of phytochemicals derived from glucosinolates. Eur J Nutr. 2008 May;47 Suppl 273-88. Huang AC, Lin TP, Weng YS, Ho YT, Lin HJ, Huang LJ, Kuo SC, Chung JG. Ethyl 2- [N-m-chlorobenzyl- (2''-methyl)] anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (JOT01006) induces apoptosis in human cervical cancer HeLa cells. Anticancer Res. 2007 Jul-Aug;27(4B):2505-14. Hwang ES, Lee HJ. Benzyl isothiocyanate inhibits metalloproteinase-2/-9 expression by suppressing the mitogen-activated protein kinase in SK-Hep1 human hepatoma cells. Food Chem Toxicol. 2008 Jul;46(7):2358-64. Kagan VE, Bayir HA, Belikova NA, Kapralov O, Tyurina YY, Tyurin VA, Jiang J, Stoyanovsky DA, Wipf P, Kochanek PM, Greenberger JS, Pitt B, Shvedova AA, Borisenko G. Cytochrome c/cardiolipin relations in mitochondria: a kiss of death. Free Radic Biol Med. 2009 Jun 1;46(11):1439-53. Kanu OO, Hughes B, Di C, Lin N, Fu J, Bigner DD, Yan H, Adamson C. Glioblastoma Multiforme Oncogenomics and Signaling Pathways. Clin Med Oncol. 2009 Apr 8;339-52. Kim SJ, Min HY, Chung HJ, Park EJ, Hong JY, Kang YJ, Shin DH, Jeong LS, Lee SK. Inhibition of cell proliferation through cell cycle arrest and apoptosis by thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, in human lung cancer cells. Cancer Lett. 2008 Jun 18;264(2):309-15. Krempler A, Deckbar D, Jeggo PA, Lobrich M. An imperfect G2M checkpoint contributes to chromosome instability following irradiation of S and G2 phase cells. Cell Cycle. 2007 Jul 15;6(14):1682-6. Kumar A, D''Souza SS, Tickoo S, Salimath BP, Singh HB. Antiangiogenic and proapoptotic activities of allyl isothiocyanate inhibit ascites tumor growth in vivo. Integr Cancer Ther. 2009 Mar;8(1):75-87. Kuo HM, Tsai HC, Lin YL, Yang JS, Huang AC, Yang MD, Hsu SC, Chung MC, Gibson Wood W, Chung JG. Mitochondrial-dependent caspase activation pathway is involved in baicalein-induced apoptosis in human hepatoma J5 cells. Int J Oncol. 2009 Oct;35(4):717-24. Kushad MM, Brown AF, Kurilich AC, Juvik JA, Klein BP, Wallig MA, Jeffery EH. Variation of glucosinolates in vegetable crops of Brassica oleracea. J Agric Food Chem. 1999 Apr;47(4):1541-8. Lin HL, Yang JS, Yang JH, Fan SS, Chang WC, Li YC, Chung JG. The role of Ca2+ on the DADS-induced apoptosis in mouse-rat hybrid retina ganglion cells (N18). Neurochem Res. 2006 Mar;31(3):383-93. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009 Mar;9(3):153-66. Murgia M, Giorgi C, Pinton P, Rizzuto R. Controlling metabolism and cell death: at the heart of mitochondrial calcium signalling. J Mol Cell Cardiol. 2009 Jun;46(6):781-8. Nakamura Y. Chemoprevention by isothiocyanates: molecular basis of apoptosis induction. Forum Nutr. 2009 61170-81. Packard BZ, Toptygin DD, Komoriya A, Brand L. Profluorescent protease substrates: intramolecular dimers described by the exciton model. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11640-5. Petit E, Oliver L, Vallette FM. The mitochondrial outer membrane protein import machinery: a new player in apoptosis? Front Biosci. 2009 14(3563-70. Rimando AM, Suh N. Natural products and dietary prevention of cancer. Mol Nutr Food Res. 2008 Jun;52 Suppl 1(S5. Saelens X, Festjens N, Vande Walle L, van Gurp M, van Loo G, Vandenabeele P. Toxic proteins released from mitochondria in cell death. Oncogene. 2004 Apr 12;23(16):2861-74. Sanchez-Munoz A, Perez-Ruiz E, Mendiola Fernandez C, Alba Conejo E, Gonzalez-Martin A. Current status of anti-angiogenic agents in the treatment of ovarian carcinoma. Clin Transl Oncol. 2009 Sep;11(9):589-95. Schwartz GK, Shah MA. Targeting the cell cycle: a new approach to cancer therapy. J Clin Oncol. 2005 Dec 20;23(36):9408-21. Smith T, Musk SR, Johnson IT. Allyl isothiocyanate selectively kills undifferentiated HT29 cells in vitro and suppresses aberrant crypt foci in the colonic mucosa of rats. Biochem Soc Trans. 1996 Aug;24(3):381S. Smith TK, Lund EK, Parker ML, Clarke RG, Johnson IT. Allyl-isothiocyanate causes mitotic block, loss of cell adhesion and disrupted cytoskeletal structure in HT29 cells. Carcinogenesis. 2004 Aug;25(8):1409-15. Srivastava SK, Xiao D, Lew KL, Hershberger P, Kokkinakis DM, Johnson CS, Trump DL, Singh SV. Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo. Carcinogenesis. 2003 Oct;24(10):1665-70. Tang L, Zhang Y. Dietary isothiocyanates inhibit the growth of human bladder carcinoma cells. J Nutr. 2004 Aug;134(8):2004-10. Thornberry NA, Lazebnik Y. Caspases: enemies within. Science. 1998 Aug 28;281(5381):1312-6. Vazquez A, Bond EE, Levine AJ, Bond GL. The genetics of the p53 pathway, apoptosis and cancer therapy. Nat Rev Drug Discov. 2008 Dec;7(12):979-87. Wajant H. The Fas signaling pathway: more than a paradigm. Science. 2002 May 31;296(5573):1635-6. Wang DY, Yeh CC, Lee JH, Hung CF, Chung JG. Berberine inhibited arylamine N-acetyltransferase activity and gene expression and DNA adduct formation in human malignant astrocytoma (G9T/VGH) and brain glioblastoma multiforms (GBM 8401) cells. Neurochem Res. 2002 Sep;27(9):883-9. Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med. 2008 Jul 31;359(5):492-507. Xiao D, Srivastava SK, Lew KL, Zeng Y, Hershberger P, Johnson CS, Trump DL, Singh SV. Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosis. Carcinogenesis. 2003 May;24(5):891-7. Yang JS, Chen GW, Hsia TC, Ho HC, Ho CC, Lin MW, Lin SS, Yeh RD, Ip SW, Lu HF, Chung JG. Diallyl disulfide induces apoptosis in human colon cancer cell line (COLO 205) through the induction of reactive oxygen species, endoplasmic reticulum stress, caspases casade and mitochondrial-dependent pathways. Food Chem Toxicol. 2009 Jan;47(1):171-9. Yang JS, Hour MJ, Kuo SC, Huang LJ, Lee MR. Selective induction of G2/M arrest and apoptosis in HL-60 by a potent anticancer agent, HMJ-38. Anticancer Res. 2004 May-Jun;24(3a):1769-78. Zhang Y. Allyl isothiocyanate as a cancer chemopreventive phytochemical. Mol Nutr Food Res. 2010 Jan;54(1):127-35. Zhang Y, Tang L, Gonzalez V. Selected isothiocyanates rapidly induce growth inhibition of cancer cells. Mol Cancer Ther. 2003 Oct;2(10):1045-52. Zhao D, Gong T, Fu Y, Nie Y, He LL, Liu J, Zhang ZR. Lyophilized Cheliensisin A submicron emulsion for intravenous injection: characterization, in vitro and in vivo antitumor effect. Int J Pharm. 2008 Jun 5;357(1-2):139-47. Ziegler DS, Kung AL. Therapeutic targeting of apoptosis pathways in cancer. Curr Opin Oncol. 2008 Jan;20(1):97-103. 第二部分 Annabi B, Currie JC, Moghrabi A, Beliveau R. Inhibition of HuR and MMP-9 expression in macrophage-differentiated HL-60 myeloid leukemia cells by green tea polyphenol EGCg. Leuk Res. 2007 Sep;31(9):1277-84. Azam S, Hadi N, Khan NU, Hadi SM. Prooxidant property of green tea polyphenols epicatechin and epigallocatechin-3-gallate: implications for anticancer properties. Toxicol In Vitro. 2004 Oct;18(5):555-61. Bose M, Lambert JD, Ju J, Reuhl KR, Shapses SA, Yang CS. The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat-fed mice. J Nutr. 2008 Sep;138(9):1677-83. Chen YC, Lu PH, Pan SL, Teng CM, Kuo SC, Lin TP, Ho YF, Huang YC, Guh JH. Quinolone analogue inhibits tubulin polymerization and induces apoptosis via Cdk1-involved signaling pathways. Biochem Pharmacol. 2007 Jun 30;74(1):10-9. Chiang JH, Yang JS, Ma CY, Yang MD, Huang HY, Hsia TC, Kuo HM, Wu PP, Lee TH, Chung JG. Danthron, an anthraquinone derivative, induces DNA damage and caspase cascades-mediated apoptosis in SNU-1 human gastric cancer cells through mitochondrial permeability transition pores and Bax-triggered pathways. Chem Res Toxicol. 2011 Jan 14;24(1):20-9. Chung JG, Yang JS, Huang LJ, Lee FY, Teng CM, Tsai SC, Lin KL, Wang SF, Kuo SC. Proteomic approach to studying the cytotoxicity of YC-1 on U937 leukemia cells and antileukemia activity in orthotopic model of leukemia mice. Proteomics. 2007 Sep;7(18):3305-17. Collins QF, Liu HY, Pi J, Liu Z, Quon MJ, Cao W. Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, suppresses hepatic gluconeogenesis through 5''-AMP-activated protein kinase. J Biol Chem. 2007 Oct 12;282(41):30143-9. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 1997 Oct 17;91(2):231-41. Davenport A, Frezza M, Shen M, Ge Y, Huo C, Chan TH, Dou QP. Celastrol and an EGCG pro-drug exhibit potent chemosensitizing activity in human leukemia cells. Int J Mol Med. 2010 Mar;25(3):465-70. De Martino L, Marfe G, Longo M, Fiorito F, Montagnaro S, Iovane V, Decaro N, Pagnini U. Bid cleavage, cytochrome c release and caspase activation in canine coronavirus-induced apoptosis. Vet Microbiol. 2010 Feb 24;141(1-2):36-45. Dethlefsen LA, Prewitt JM, Mendelsohn ML. Analysis of tumor growth curves. J Natl Cancer Inst. 1968 Feb;40(2):389-405. Dhote R, Beuzeboc P, Thiounn N, Flam T, Zerbib M, Christoforov B, Debre B. High incidence of brain metastases in patients treated with an M-VAC regimen for advanced bladder cancer. Eur Urol. 1998 33(4):392-5. El Golli Bennour E, Rodriguez-Enfedaque A, Bouaziz C, Ladjimi M, Renaud F, Bacha H. Toxicities induced in cultured human hepatocarcinoma cells exposed to ochratoxin A: oxidative stress and apoptosis status. J Biochem Mol Toxicol. 2009 Mar-Apr;23(2):87-96. Fujii H, Nishioka H, Wakame K, Magnuson BA, Roberts A. Acute, subchronic and genotoxicity studies conducted with Oligonol, an oligomerized polyphenol formulated from lychee and green tea extracts. Food Chem Toxicol. 2008 Dec;46(12):3553-62. Gillespie K, Kodani I, Dickinson DP, Ogbureke KU, Camba AM, Wu M, Looney S, Chu TC, Qin H, Bisch F, Sharawy M, Schuster GS, Hsu SD. Effects of oral consumption of the green tea polyphenol EGCG in a murine model for human Sjogren''s syndrome, an autoimmune disease. Life Sci. 2008 Oct 24;83(17-18):581-8. Guo S, Yang S, Taylor C, Sonenshein GE. Green tea polyphenol epigallocatechin-3 gallate (EGCG) affects gene expression of breast cancer cells transformed by the carcinogen 7,12-dimethylbenz[a]anthracene. J Nutr. 2005 Dec;135(12 Suppl):2978S-2986S. Hara Y, Fujino M, Takeuchi M, Li XK. Green-tea polyphenol (-)-epigallocatechin-3-gallate provides resistance to apoptosis in isolated islets. J Hepatobiliary Pancreat Surg. 2007 14(5):493-7. Hsu S, Lewis J, Singh B, Schoenlein P, Osaki T, Athar M, Porter AG, Schuster G. Green tea polyphenol targets the mitochondria in tumor cells inducing caspase 3-dependent apoptosis. Anticancer Res. 2003 Mar-Apr;23(2B):1533-9. Huang CH, Tsai SJ, Wang YJ, Pan MH, Kao JY, Way TD. 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 Sep;53(9):1156-65. Jacquemin G, Shirley S, Micheau O. Combining naturally occurring polyphenols with TNF-related apoptosis-inducing ligand: a promising approach to kill resistant cancer cells? Cell Mol Life Sci. 2010 Sep;67(18):3115-30. Ji BC, Hsu WH, Yang JS, Hsia TC, Lu CC, Chiang JH, Yang JL, Lin CH, Lin JJ, Suen LJ, Gibson Wood W, Chung JG. Gallic acid induces apoptosis via caspase-3 and mitochondrion-dependent pathways in vitro and suppresses lung xenograft tumor growth in vivo. J Agric Food Chem. 2009 Aug 26;57(16):7596-604. Kaji H, Tsuji T, Mawuenyega KG, Wakamiya A, Taoka M, Isobe T. Profiling of Caenorhabditis elegans proteins using two-dimensional gel electrophoresis and matrix assisted laser desorption/ionization-time of flight-mass spectrometry. Electrophoresis. 2000 May;21(9):1755-65. Khan N, Mukhtar H. Multitargeted therapy of cancer by green tea polyphenols. Cancer Lett. 2008 Oct 8;269(2):269-80. Konishi H, Tanaka M, Takemura Y, Matsuzaki H, Ono Y, Kikkawa U, Nishizuka Y. Activation of protein kinase C by tyrosine phosphorylation in response to H2O2. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11233-7. Kotwal S, Munro N. Radiotherapy in localized bladder cancer: what is the evidence? Curr Opin Urol. 2010 Sep;20(5):426-31. Kuo CT, Hsu MJ, Chen BC, Chen CC, Teng CM, Pan SL, Lin CH. Denbinobin induces apoptosis in human lung adenocarcinoma cells via Akt inactivation, Bad activation, and mitochondrial dysfunction. Toxicol Lett. 2008 Feb 28;177(1):48-58. Kuo JH, Chu YL, Yang JS, Lin JP, Lai KC, Kuo HM, Hsia TC, Chung JG. Cantharidin induces apoptosis in human bladder cancer TSGH 8301 cells through mitochondria-dependent signal pathways. Int J Oncol. 2010 Nov;37(5):1243-50. Lahiry L, Saha B, Chakraborty J, Adhikary A, Mohanty S, Hossain DM, Banerjee S, Das K, Sa G, Das T. Theaflavins target Fas/caspase-8 and Akt/pBad pathways to induce apoptosis in p53-mutated human breast cancer cells. Carcinogenesis. 2010 Feb;31(2):259-68. Lam YW, Evans VC, Heesom KJ, Lamond AI, Matthews DA. Proteomics analysis of the nucleolus in adenovirus-infected cells. Mol Cell Proteomics. 2010 Jan;9(1):117-30. Levites Y, Amit T, Mandel S, Youdim MB. Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (-)-epigallocatechin-3-gallate. FASEB J. 2003 May;17(8):952-4. Li Y, Yuan YY, Meeran SM, Tollefsbol TO. Synergistic epigenetic reactivation of estrogen receptor-alpha (ERalpha) by combined green tea polyphenol and histone deacetylase inhibitor in ERalpha-negative breast cancer cells. Mol Cancer. 2010 9(274. Lin CC, Yang JS, Chen JT, Fan S, Yu FS, Yang JL, Lu CC, Kao MC, Huang AC, Lu HF, Chung JG. Berberine induces apoptosis in human HSC-3 oral cancer cells via simultaneous activation of the death receptor-mediated and mitochondrial pathway. Anticancer Res. 2007 Sep-Oct;27(5A):3371-8. Lin SS, Huang HP, Yang JS, Wu JY, Hsia TC, Lin CC, Lin CW, Kuo CL, Gibson Wood W, Chung JG. DNA damage and endoplasmic reticulum stress mediated curcumin-induced cell cycle arrest and apoptosis in human lung carcinoma A-549 cells through the activation caspases cascade- and mitochondrial-dependent pathway. Cancer Lett. 2008 Dec 8;272(1):77-90. Liu L, Lai CQ, Nie L, Ordovas J, Band M, Moser L, Meydani M. The modulation of endothelial cell gene expression by green tea polyphenol-EGCG. Mol Nutr Food Res. 2008 Oct;52(10):1182-92. Lu CC, Yang JS, Huang AC, Hsia TC, Chou ST, Kuo CL, Lu HF, Lee TH, Wood WG, Chung JG. Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells. Mol Nutr Food Res. 2010a Jul;54(7):967-76. Lu HF, Lai KC, Hsu SC, Lin HJ, Yang MD, Chen YL, Fan MJ, Yang JS, Cheng PY, Kuo CL, Chung JG. Curcumin induces apoptosis through FAS and FADD, in caspase-3-dependent and -independent pathways in the N18 mouse-rat hybrid retina ganglion cells. Oncol Rep. 2009 Jul;22(1):97-104. Lu HF, Wang HL, Chuang YY, Tang YJ, Yang JS, Ma YS, Chiang JH, Lu CC, Yang JL, Lai TY, Wu CC, Chung JG. Danthron induced apoptosis through mitochondria- and caspase-3-dependent pathways in human brain glioblastoma multiforms GBM 8401 cells. Neurochem Res. 2010b Mar;35(3):390-8. Lu KH, Lue KH, Chou MC, Chung JG. Paclitaxel induces apoptosis via caspase-3 activation in human osteogenic sarcoma cells (U-2 OS). J Orthop Res. 2005 Sep;23(5):988-94. Miyake H, Hara I, Yamanaka K, Gohji K, Arakawa S, Kamidono S. Overexpression of Bcl-2 enhances metastatic potential of human bladder cancer cells. Br J Cancer. 1999 Apr;79(11-12):1651-6. Natrajan R, Louhelainen J, Williams S, Laye J, Knowles MA. High-resolution deletion mapping of 15q13.2-q21.1 in transitional cell carcinoma of the bladder. Cancer Res. 2003 Nov 15;63(22):7657-62. Natsume H, Adachi S, Takai S, Tokuda H, Matsushima-Nishiwaki R, Minamitani C, Yamauchi J, Kato K, Mizutani J, Kozawa O, Otsuka T. (-)-Epigallocatechin gallate attenuates the induction of HSP27 stimulated by sphingosine 1-phosphate via suppression of phosphatidylinositol 3-kinase/Akt pathway in osteoblasts. Int J Mol Med. 2009 Aug;24(2):197-203. Nishikawa T, Nakajima T, Moriguchi M, Jo M, Sekoguchi S, Ishii M, Takashima H, Katagishi T, Kimura H, Minami M, Itoh Y, Kagawa K, Okanoue T. A green tea polyphenol, epigalocatechin-3-gallate, induces apoptosis of human hepatocellular carcinoma, possibly through inhibition of Bcl-2 family proteins. J Hepatol. 2006 Jun;44(6):1074-82. Peng G, Wargovich MJ, Dixon DA. Anti-proliferative effects of green tea polyphenol EGCG on Ha-Ras-induced transformation of intestinal epithelial cells. Cancer Lett. 2006 Jul 18;238(2):260-70. Porter MP, Penson DF. Health related quality of life after radical cystectomy and urinary diversion for bladder cancer: a systematic review and critical analysis of the literature. J Urol. 2005 Apr;173(4):1318-22. Qin J, Xie LP, Zheng XY, Wang YB, Bai Y, Shen HF, Li LC, Dahiya R. A component of green tea, (-)-epigallocatechin-3-gallate, promotes apoptosis in T24 human bladder cancer cells via modulation of the PI3K/Akt pathway and Bcl-2 family proteins. Biochem Biophys Res Commun. 2007 Mar 23;354(4):852-7. Rane MJ, Pan Y, Singh S, Powell DW, Wu R, Cummins T, Chen Q, McLeish KR, Klein JB. Heat shock protein 27 controls apoptosis by regulating Akt activation. J Biol Chem. 2003 Jul 25;278(30):27828-35. Rieger-Christ KM, Hanley R, Lodowsky C, Bernier T, Vemulapalli P, Roth M, Kim J, Yee AS, Le SM, Marie PJ, Libertino JA, Summerhayes IC. The green tea compound, (-)-epigallocatechin-3-gallate downregulates N-cadherin and suppresses migration of bladder carcinoma cells. J Cell Biochem. 2007 Oct 1;102(2):377-88. Roura E, Andres-Lacueva C, Estruch R, Lourdes Mata Bilbao M, Izquierdo-Pulido M, Lamuela-Raventos RM. The effects of milk as a food matrix for polyphenols on the excretion profile of cocoa (-)-epicatechin metabolites in healthy human subjects. Br J Nutr. 2008 Oct;100(4):846-51. Sagara Y, Miyata Y, Nomata K, Hayashi T, Kanetake H. Green tea polyphenol suppresses tumor invasion and angiogenesis in N-butyl-(-4-hydroxybutyl) nitrosamine-induced bladder cancer. Cancer Epidemiol. 2010 Jun;34(3):350-4. Siddiqui IA, Adhami VM, Bharali DJ, Hafeez BB, Asim M, Khwaja SI, Ahmad N, Cui H, Mousa SA, Mukhtar H. Introducing nanochemoprevention as a novel approach for cancer control: proof of principle with green tea polyphenol epigallocatechin-3-gallate. Cancer Res. 2009 Mar 1;69(5):1712-6. Siddiqui IA, Malik A, Adhami VM, Asim M, Hafeez BB, Sarfaraz S, Mukhtar H. Green tea polyphenol EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-mediated apoptosis and synergistically inhibits biomarkers associated with angiogenesis and metastasis. Oncogene. 2008 Mar 27;27(14):2055-63. Sueoka N, Suganuma M, Sueoka E, Okabe S, Matsuyama S, Imai K, Nakachi K, Fujiki H. A new function of green tea: prevention of lifestyle-related diseases. Ann N Y Acad Sci. 2001 Apr;928274-80. Suganuma M, Kurusu M, Suzuki K, Tasaki E, Fujiki H. Green tea polyphenol stimulates cancer preventive effects of celecoxib in human lung cancer cells by upregulation of GADD153 gene. Int J Cancer. 2006 Jul 1;119(1):33-40. Tan CY, Ban H, Kim YH, Lee SK. The heat shock protein 27 (Hsp27) operates predominantly by blocking the mitochondrial-independent/extrinsic pathway of cellular apoptosis. Mol Cells. 2009 May 31;27(5):533-8. von Haefen C, Wendt J, Semini G, Sifringer M, Belka C, Radetzki S, Reutter W, Daniel PT, Danker K. Synthetic glycosidated phospholipids induce apoptosis through activation of FADD, caspase-8 and the mitochondrial death pathway. Apoptosis. 2011 Mar 25. Wang YC, Bachrach U. The specific anti-cancer activity of green tea (-)-epigallocatechin-3-gallate (EGCG). Amino Acids. 2002 22(2):131-43. Wheeler DS, Catravas JD, Odoms K, Denenberg A, Malhotra V, Wong HR. Epigallocatechin-3-gallate, a green tea-derived polyphenol, inhibits IL-1 beta-dependent proinflammatory signal transduction in cultured respiratory epithelial cells. J Nutr. 2004 May;134(5):1039-44. Wirth M, Plattner VE, Gabor F. Strategies to improve drug delivery in bladder cancer therapy. Expert Opin Drug Deliv. 2009 Jul;6(7):727-44. Wu PP, Kuo SC, Huang WW, Yang JS, Lai KC, Chen HJ, Lin KL, Chiu YJ, Huang LJ, Chung JG. (-)-Epigallocatechin gallate induced apoptosis in human adrenal cancer NCI-H295 cells through caspase-dependent and caspase-independent pathway. Anticancer Res. 2009 Apr;29(4):1435-42. Wu SH, Hang LW, Yang JS, Chen HY, Lin HY, Chiang JH, Lu CC, Yang JL, Lai TY, Ko YC, Chung JG. Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pathways. Anticancer Res. 2010 Jun;30(6):2125-33. Yang JS, Hour MJ, Huang WW, Lin KL, Kuo SC, Chung JG. MJ-29 inhibits tubulin polymerization, induces mitotic arrest, and triggers apoptosis via cyclin-dependent kinase 1-mediated Bcl-2 phosphorylation in human leukemia U937 cells. J Pharmacol Exp Ther. 2010 Aug;334(2):477-88. Zapatero A, Martin de Vidales C, Arellano R, Bocardo G, Perez M, Rios P. Updated results of bladder-sparing trimodality approach for invasive bladder cancer. Urol Oncol. 2010 Jul-Aug;28(4):368-74. Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell. 1996 Nov 15;87(4):619-28. Zhang M, Zhao X, Zhang X, Holman CD. Possible protective effect of green tea intake on risk of adult leukaemia. Br J Cancer. 2008 Jan 15;98(1):168-70.
摘要: 
飲食與癌症治療息息相關,近年研究顯示適當的飲食可以降低癌症的發生率,這些天然飲食中的活性成分,可分為油溶性與水溶性兩類,本文第一部分談討油溶性成分烯丙基異硫氰酸酯 (Allyl isothiocyanate, AITC) 透過粒線體依賴性路徑引發人類腦惡性膠質瘤GBM 8401細胞產生G2/M期停滯及細胞凋亡。第二部分利用蛋白質體學研究水溶性成分表沒食子兒茶素沒食子酸酯 (Epigallocatechin gallate; EGCG) 挑起台灣特定人類膀胱癌TSGH-8301細胞產生的細胞凋亡。
第一部分:異硫氰酸酯 (isothiocyanates; ITCs) 以硫代葡萄糖苷 (glucosinolates)形式存在於不同的十字花科 (cruciferous)蔬菜中。其中烯丙基異硫氰酸酯 (allyl isothiocyanate; AITC) 是一種常見的自然產生異硫氰酸酯 (ITCs)。最近的研究顯示AITC在離體試驗 (in vitro)中可抑制人類血癌HL-60細胞、膀胱癌UM-UC-3細胞和結腸癌HT-29細胞的存活率。本研究中,我們發現AITC能夠劑量依賴性明顯地減低人類腦惡性膠質瘤GBM 8401細胞的增殖和存活率,以24小時處理其最大抑制50%濃度 (the half maximal inhibitory concentration; IC50)為9.25±0.69 μM。在細胞週期分佈分析也顯示,AITC顯著地誘導GBM 8401細胞中G2/M期停滯和sub-G1期增加 (細胞凋亡族群)。以CDK1活性測定和西方墨點法分析發現AITC能明顯降低CDK1/cyclin B的活性和蛋白層次的影響。藉由形態的檢測及DAPI染色觀察證實AITC能誘導產生細胞凋亡。經預處理特異性caspase-3抑制劑 (Z-DEVE-FMK) 和caspase-9抑制劑 (Z-LEHD-FMK)可以顯著地降低GBM 8401細胞中casapse-3和-9的活性。由西方墨點法和比色法 (colorimetric assay)檢測也顯示AITC造成時間依賴性地增加細胞質內cytochrome c、pro-caspase-9、Apaf-1、AIF、Endo G蛋白層次且刺激caspase-9和-3活性。由我們的結果推測AITC是一種具有潛力能抗人腦惡性膠質瘤的藥物,且它可先誘導細胞週期停滯後造成細胞凋亡現象的產生。
第二部分:表沒食子兒茶素沒食子酸酯 (epigallocatechin-3-gallate; EGCG)是一種存在於綠茶中的多酚類成分,有研究指出在離體 (in vitro)和活體 (in vivo)實驗中可抑制癌細胞的生長。然而,在台灣特定的人類膀胱癌細胞試驗上是有限的且無良好的研究。因此,我們的研究著重於評估EGCG在台灣特定人類膀胱癌TSGH-8301細胞離體和活體中引發的細胞凋亡及其相關分子機制的探討。在活體研究中,EGCG在裸小鼠動物模式上可抑制異種移植 (xenograft) TSGH-8301腫瘤大小。在離體研究中,結果包括:EGCG影響TSGH-8301細胞形態上的改變和抑制其生長且有劑量和時間依存性。再者,在EGCG處理TSGH-8301細胞中可使sub-G1族群出現和活化caspase-9和-3活性。此外,使用caspase-9抑制劑 (Z-LEHD-FMK)和caspase-3抑制劑 (Z-DEVD-FMK) 分別能夠降低EGCG刺激的caspase-9和-3活性。TSGH-8301細胞在處理EGCG後導致粒線體膜電位 (mitochondrial membrane potential; ΔΨm)下降與促使cytochrome c、Apaf-1、caspase-9和-3蛋白質層次增加。由蛋白質體學分析發現EGCG在TSGH-8301細胞中影響多種蛋白質的表現,包括:熱休克蛋白27 (HSP27)、Porin、Tropomyosin 3 isoform 2、Prohibitin和keratin 5、14、17等。EGCG還能抑制AKT激酶活性和蛋白層次及改變Bcl-2家族相關的蛋白質層次的影響,如:Bcl-2、Bax、BAD和p-BAD。根據上述發現顯示,EGCG在TSGH-8301細胞中挑起的細胞凋亡主要藉由針對AKT和HSP27與調控p-BAD後,導致活化內在細胞凋亡連鎖路徑。

Recent studies have shown there is a strong link between diet and cancer. Moreover, these studies have shown that certain foods can lower the chances of getting cancer. In general, there are two active parts in these foods, namely pertaining to oil solubility or water solubility. The first part of this paper discusses how oil soluble Allyl isothiocyanate triggers G2/M phase arrest and apoptosis in human brain malignant glioma GBM 8401 cells, through a mitochondria-dependent pathway. The second part uses a proteomic approach to studying water soluble epigallocatechin gallate-provoked apoptosis of TSGH-8301 in human urinary bladder carcinoma cells: roles of AKT and heat shock protein 27-modulated intrinsic apoptotic pathways.
PART I. Isothiocyanates (ITCs) are present as glucosinolates in various cruciferous vegetables. Allyl isothiocyanate (AITC) is one the common naturally occurring isothiocyanates. Recent studies have shown that AITC significantly inhibited survival of leukemia HL-60, bladder cancer UM-UC-3 and colon cancer HT-29 cancer cells in vitro. In this study, we demonstrate that AITC significantly decreased proliferation and viability of human brain malignant glioma GBM 8401 cells in a dose-dependent manner with the half maximal inhibitory concentration (IC50) 9.25±0.69 μM for 24 h-treatment. The analysis of cell cycle distribution also showed that AITC induced significantly G2/M arrest and sub-G1 phase (apoptotic population) in GBM 8401 cells. AITC markedly reduced the CDK1/cyclin B activity and protein levels by CDK1 activity assay and Western blot analysis. AITC-induced apoptotic cell death and this evidence was confirmed by morphological assessment and DAPI staining. Pretreatment with specific inhibitors of caspase-3 (Z-DEVE-FMK) and -9 (Z-LEHD-FMK) significantly reduced the casapse-3 and -9 activities in GBM 8401 cells. Western blot analysis and colorimetric assays also displayed that AITC caused a time-dependent increase in cytosolic cytochrome c, pro-caspase-9, Apaf-1, AIF, Endo G and the stimulated caspase-9 and -3 activity. Our results suggest that AITC is a potent anti-human brain malignant glioma drug and it shows a remarkable action on cell cycle arrest before commitment for apoptosis is reached.
PART II. Epigallocatechin-3-gallate (EGCG), a polyphenol constituent presented in green tea, has shown to inhibit the growth of cancer cells in vitro and in vivo. However, the studies regarding Taiwan specific human bladder carcinoma cells are limited and not well investigated. Hence, our study focused on evaluation of EGCG-triggered apoptosis in Taiwan specific human urinary bladder carcinoma TSGH-8301 cells in vivo and in vitro as well as its related molecular mechanisms. In in-vivo study, EGCG inhibited xenograft tumor size of TSGH-8301 cells in a nude mouse model. In in-vitro study, the results included that EGCG affected morphological changes and increased a growth inhibitory in a dose- and time-dependent manner in TSGH-8301 cells. Furthermore, sub-G1 populations were shown and caspase-9 and -3 activities were stimulated in EGCG-treated TSGH-8301 cells. Moreover, a caspase-9 inhibitor (Z-LEHD-FMK) and a caspase-3 inhibitor (Z-DEVD-FMK) are able to reduce EGCG-stimulated caspase-9 and -3 activities, respectively. Loss of mitochondrial membrane potential (ΔΨm) resulted in the increases of protein levels in cytochrome c, Apaf-1, caspase-9 and -3 in TSGH-8301 cells after exposure to EGCG. Proteomic analysis discovered that EGCG affected the expression levels of various proteins, including HSP27, porin, tropomyosin 3 isoform 2, prohibitin and keratin 5, 14, 17 in TSGH-8301 cells. EGCG also suppressed AKT kinase activity and protein levels as well as altered Bcl-2 family-related protein levels such as Bcl-2, Bax, BAD and p-BAD. Based on the above findings, this study suggest that EGCG-provoked apoptotic death in TSGH-8301 cells is mediated through targeting the AKT and HSP27 and modulating the p-BAD, leading to activate the intrinsic apoptotic cascade pathway.
URI: http://hdl.handle.net/11455/12957
其他識別: U0005-2001201211142000
Appears in Collections:獸醫學系所

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