(3.237.178.91) 您好!臺灣時間:2021/03/04 09:28
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:鄭凱澤
研究生(外文):Kai-Tse Cheng
論文名稱:聚球藻藻藍素對人類肝癌細胞株Hep G2之影響
論文名稱(外文):The effect of phycocyanin from Synechococcus sp. U2 on human hepatocellular carcinoma cell line Hep G2
指導教授:廖遠東
指導教授(外文):Ean-Tun Liaw
學位類別:碩士
校院名稱:國立屏東科技大學
系所名稱:食品科學系所
學門:農業科學學門
學類:食品科學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:113
中文關鍵詞:聚球藻藻藍素細胞凋亡肝癌細胞株
外文關鍵詞:Synechococcus sp. U2phycocyanin (CPC)cell apoptosisHep G2 cell line
相關次數:
  • 被引用被引用:0
  • 點閱點閱:145
  • 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:0
保健食品在二十一世紀將持續獨領風騷,佔全球食品市場之重要地位,而水產保健食品則剛剛嶄露頭角極具開發潛力。聚球藻屬於藍綠藻,其富含的藻藍素為一光吸收色素-蛋白質複合體,已知具有抗氧化、抗發炎及抗癌的能力。本研究著重於從聚球藻中純化藻藍素進行抗腫瘤特性之評估,藉由下列方法:MTT assay、細胞型態變化、細胞凋亡的分析,探討藻藍素濃度及作用時間對腫瘤細胞的影響。實驗結果顯示,可以藉由添加溶菌酶結合凍結-解凍來進行萃取,並利用疏水性層析管柱與陰離子交換樹脂來純化藻藍素,回收率可達56%,並於1克的聚球藻粉末中可得到高純度的藻藍素3毫克。電泳分析結果證明,純化得到的藻藍素分子量為103 kDa,且是由分子量分別為20.4 kDa與18.5 kDa之次分子所組成。而細胞實驗顯示以500 μg/mL的藻藍素處理72小時後,可使Hep G2細胞的增殖減少74%,而其IC50値為299.1 µg/mL。而以倒立式位相差顯微鏡觀察發現細胞型態產生皺縮且形成群聚的圓形細胞。接著進一步利用流式細胞儀進行分析,細胞週期方面,結果指出經500 μg/mL的藻藍素處理72小時後,sub-G1期百分比達到20.16±0.57%。Annexin V-PI雙染分析則是以不同濃度藻藍素處理72小時後,細胞發生早期凋亡的比例介於5.39±0.3% ~ 12.62±0.69%。此外,在caspase-3活性分析方面發現處理之後活性增加6倍,其比例由2.99±0.58%增加至20.04±0.39%。
由以上的結果得知,藻藍素確實可以使Hep G2細胞走向凋亡。

Accordingly, nutraceutical will continuously leading the brand and position a critical issue of the global food market, while functional food derived from seafood just explode the highlight and exhibit a great potential at this special field. Synechococcus sp., a member of cyanobacteria family, containing phycocyanin (CPC) is one of the major light harvesting pigment-protein which exhibiting diverse antioxidant, anti-inflammatory and anticancerous properties. The main purpose of the current study is assessment of antitumor activity of CPC from Synechococcus sp. U2. The measurement of dose-dependent, and time course effect on antitumor activity of phycocyanin can be depicted by MTT assay, microscopic observation and cell apoptosis assay, respectively. The results showed that CPC was extracted with lysozyme and by freezing-thawing cycles, and purified by hydrophobic interaction chromatography with butyl sepharose column and anion chromatography using DEAE sepharose resin. The recovery efficiency of CPC from crude extract was above 56%. Three milligram pure CPC was obtained from 1 g of dried cell mass and the purity ratio (A620/A280) was 4.43.
The molecular mass of purified CPC was 103 kDa and has two subunits with apparent molecular mass of 20.4 and 18.5 kDa respectively by electrophoresis technology. In cell, the results indicated that 74% decrease in the proliferation of Hep G2 cells when treated with 500 µg/mL CPC up to 72 hrs and the IC50 was 299.1 µg/mL. By reverse phase microscope, cell morphology changed in shrinkaged and cluster of round cells were observed. The Hep G2 cell treated with CPC analyzed by Flow Cytometry suggested that in cell cycle, cells treated with 500 µg/mL CPC for 72h showed 20.16±0.57% in sub-G1. In annexin V-PI assay, the data suggested that 5.39±0.3% to 12.62±0.69% early apoptosis cells can be found when CPC were employed for 72 hours. Furthermore, the results demonstrated that the caspase 3 activity was enhanced by 6-fold from 2.99±0.58% to 20.04±0.39% when treated with the subject. Conclusively, the present study illustrated that CPC followed apoptosis pathway on Hep G2 cell lines.
中文摘要 I
英文摘要 III
謝 誌 V
目 錄 VI
1. 前言 1
2. 文獻回顧 3
2.1 藻類 3
2.1.1 海洋藻類 5
2.1.2 藍藻 6
2.1.3 藍藻的應用 7
2.1.4 聚球藻 10
2.2 藻藍素 10
2.2.1 藻藍素之應用 13
2.2.2 藻藍素之生理活性 13
2.2.2.1 抗氧化活性 13
2.2.2.2 抗發炎活性 14
2.2.2.3 保護肝臟 15
2.2.2.4 抗腫瘤活性 16
2.3 肝癌 17
2.3.1 肝癌高風險群 17
2.3.2 肝癌症狀 18
2.3.3 肝癌診斷 19
2.3.4 肝癌治療 19
2.3.5 肝癌預防 22
2.4 常用之抗癌藥物 23
2.4.1 Doxorubicin 23
2.4.2 5-flurouracil 24
2.5 細胞週期 26
2.5.1 細胞週期在癌症治療上的應用 28
2.6 細胞死亡 28
2.6.1 細胞壞死 28
2.6.2 細胞凋亡 29
2.6.2.1 細胞凋亡之分期 30
2.6.2.2 細胞凋亡之途徑 32
2.6.2.2.1 死亡接受體途徑 33
2.6.2.2.2 粒腺體途徑 33
3. 材料與方法 37
3.1 實驗設計 37
3.2 實驗材料來源 39
3.2.1 聚球藻來源 39
3.2.2 細胞株來源 39
3.3 實驗試藥及設備 39
3.3.1 藻藍素純化試藥 39
3.3.2 電泳分析試藥 39
3.3.3 細胞培養及分析試藥與套組 40
3.3.4 常用儀器設備 40
3.4 實驗方法 41
3.4.1 聚球藻培養 41
3.4.2 聚球藻前處理 42
3.4.3 藻藍素分離與純化 42
3.4.3.1 聚球藻粗萃液製備 42
3.4.3.2 疏水性層析 42
3.4.3.3 陰離子交換層析 43
3.4.3.4 蛋白質含量測定 43
3.4.3.5 藻藍素含量測定 43
3.4.3.6 純化總表製作 44
3.4.4 分子量測定 44
3.4.4.1 電泳樣品處理 44
3.4.4.2 電泳分析試劑配製 44
3.4.4.3 電泳膠體製備 45
3.4.4.4 電泳操作步驟 47
3.4.5 細胞培養 47
3.4.5.1 培養基配製 47
3.4.5.2 緩衝溶液配製 48
3.4.5.3 細胞解凍 48
3.4.5.4 細胞繼代培養 48
3.4.5.5 細胞計數 49
3.4.5.6 細胞冷凍保存 49
3.4.6 細胞試驗 50
3.4.6.1 細胞存活率測試 50
3.4.6.2 細胞型態觀察 50
3.4.6.3 流式細胞儀分析 50
3.4.6.3.1 細胞週期分析 51
3.4.6.3.2 Annexin V-PI雙染分析 51
3.4.6.3.3 Caspase 3蛋白酶活性分析 52
3.4.7 統計分析 52
4. 結果與討論 53
4.1 聚球藻培養與前處理 53
4.2 藻藍素之純化 57
4.2.1 粗萃取液製備 57
4.2.2 疏水性交換層析 58
4.2.3 陰離子交換層析 60
4.2.4 純化總表 62
4.3 分子量測定 67
4.3.1 Native-PAGE 67
4.3.2 SDS-PAGE 67
4.4 細胞試驗 70
4.4.1 細胞存活率測試-MTT assay 70
4.4.2 細胞型態觀察 75
4.4.3 流式細胞儀分析 82
4.4.3.1 細胞週期分析 82
4.4.3.2 Annexin V-PI雙染分析 85
4.4.3.3 Caspase 3蛋白酶活性分析 93
5. 結論 98
參考文獻 99
作者簡介 113

圖表目錄
圖 1、藻膽色體其概要構造圖 12
圖 2、藻藍素之bilin發色基團與膽紅素之化學結構 14
圖 3、Doxorubicin化學結構式 25
圖 4、5-flurouracil化學結構式 25
圖 5、細胞週期 27
圖 6、細胞凋亡與細胞壞死 30
圖 7、細胞凋亡之三種途徑 32
圖 8、細胞凋亡之死亡接受器途徑 35
圖 9、細胞凋亡之粒線體途徑 36
圖 10、藻藍素抗腫瘤活性之實驗設計 38
圖 11、聚球藻之菌種觀察:聚球藻培養液 54
圖 12、聚球藻粉末外觀 55
圖 13、 Synechococcus sp. U2中藻藍素之butyl-sepharose管柱層析圖 59
圖 14、 Synechococcus sp. U2中藻藍素之DEAE-sepharose管柱層析圖 61
圖 15、A:聚球藻培養液;B:經純化後所得之藻藍素純化液 65
圖 16、經純化後之藻藍素吸收波長曲線圖 66
圖 17、Synechococcus sp. U2中藻藍素之Native-PAGE電泳圖 68
圖 18、Synechococcus sp. U2中藻藍素之SDS-PAGE電泳圖 69
圖 19、聚球藻中藻藍素對人類肝癌細胞株Hep G2之毒殺效果 72
圖 20、不同濃度之藻藍素處理Hep G2細胞24小時後的細胞型態變化 (200x) 77
圖 21、不同濃度之藻藍素處理Hep G2細胞48小時後的細胞型態變化 (200x) 78
圖 22、不同濃度之藻藍素處理Hep G2細胞72小時後的細胞型態變化 (200x) 79
圖 23、經5FU處理不同時間後之AGS細胞的型態變化 (200x) 80
圖 24、不同濃度之藻藍素處理AGS細胞後的細胞型態變化 (200x) 81
圖 25、不同濃度之藻藍素處理Hep G2細胞24小時後annexin V-PI分析 87
圖 26、不同濃度之藻藍素處理Hep G2細胞48小時後annexin V-PI分析 88
圖 27、不同濃度之藻藍素處理Hep G2細胞72小時後annexin V-PI分析 89
圖 28、不同濃度之藻藍素處理Hep G2細胞24小時後caspase 3活性變化 94
圖 29、不同濃度之藻藍素處理Hep G2細胞48小時後caspase 3活性變化 95
圖 30、不同濃度之藻藍素處理Hep G2細胞72小時後caspase 3活性變化 96

表 1、藻類主要特徵與類型 4
表 2、細胞凋亡與細胞壞死之差異 31
表 3、MN培養基 42
表 4、聚球藻粉末之產率 56
表 5、Synechococcus sp.U2藻藍素之純化總表 64
表 6、聚球藻中藻藍素對人類腫瘤細胞株Hep G2之毒殺效果 73
表 7、聚球藻中藻藍素對人類腫瘤細胞株AGS之毒殺效果 74
表 8、 以不同濃度藻藍素處理24至72小時後其Sub-G1期百分比 84
表 9、 以不同濃度藻藍素處理24小時後其細胞死亡之情形 90
表 10、以不同濃度藻藍素處理48小時後其細胞死亡之情形 91
表 11、以不同濃度藻藍素處理72小時後其細胞死亡之情形 92
表 12、以不同濃度藻藍素處理不同時間後其促凋亡蛋白產生之百分比 97
王政韋。1998。肝癌防治法。浩園文化事業有限公司。第36-115頁。台北,台灣。
李炎。2001。藍(細)菌:1種可產生氧氣的光和作用原核生物=Cyanobacteria。藝軒圖書出版社。第104-16頁。台北,台灣。
李炎。2005。藍菌研究。藝軒圖書出版社。第103-19頁。台北,台灣。
杜姿瑩、華傑。2002。產業用菌種市場潛力:細菌與藻類。財團法人工業研究所。第97-115頁。新竹,台灣。
周雪美。1987。二種單胞固氮藍綠藻之形態與生理特性的比較,師大生物學報 22: 33-43。
胡志棠。2002a。肝癌的治療(下)。當代醫學 29(4): 331-6。
胡志棠。2002a。肝癌的治療(上)。當代醫學 29(3): 203-7。
徐榮源。1998。C型肝炎與肝癌。國防醫學 27(3): 189-92。
國立台灣博物館台灣海藻資訊網。2004。海藻分類查詢系統。檢索日期:2009年3月28日。檢自:http://www.ntm.gov.tw/seaweeds/home.asp
陳建弘。2005。找回健康肝-肝炎、肝硬化、肝癌防治知識全覽。原水文化。第183-204頁。台北,台灣。
黃檀溪。1986。 藍綠藻的形態與結構。藻類之研究與應用研討會論文級專刊15: 1-21。
鄭育麟。1993。環工指標微生物。第102-7頁。復文書局。台南,台灣。
蕭辛癸。2001。利用氰細菌生產胡蘿蔔素與脂肪酸之探討。國立海洋大學食品科學系碩士論文。
Abalde J, Betancourt L, Torres E, Cid A, Barwell C. 1998. Purification and characterization of phycocyanin from marine cyanobacterium Synechococcus sp. IO9201. Plant Science 136: 109-20.
Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J. 1996. Human ICE/CED-3 protease nomenclature. Cell 87: 171.
Amit MW, Gillies MK, Ruth JM. 1997. Cyclin A message, stability varies with the cell cycle. Cell Growth and Differentiation 8: 311-8.
Araoz R, Hader DP. 1997. Ultraviolet radiation induces both degradation and synthesis of phycobilisomes in Nostoc sp. : a spectroscopic and biochemical approach. FEMS Microbiology Ecology 23: 301-13.
Beams HW, Kessel RG. 1977. Physical properties of blue-green algae: ultracentrifugation and electron microscope studies. Protoplasm 92: 229-42.
Benedetti S, Benvenuti F, Pagliarani S, Francogli S, Scoglio S, Canestrari F. 2004. Antioxidant properties of a novel phycocyanin extract from the blue-green alga Aphanizomenon flos-aquae. Life Sciences 75: 2353-62.
Bhat VB, Gaikwad WN, Madyastha KM. 1998. Hepatoprotective effect of C-phycocyanin for carbon tetrachloride and R-(+)-pulegone-mediated hepatotoxicity in rats. Biochemical and Biophysical Research Communications 249: 428-31.
Bhat VB, Madyastha KM. 2000. C-phycocyanin: a potent peroxyl radical scavenger in vivo and in vitro. Biochemical and Biophysical Research Communications 275: 20-5.
Bhat VB, Madyastha KM. 2001. Scavenging of peroxynitrite by phycocyanin and phycoanobilin from Spirulina platensis: protection against oxidative damage to DNA. Biochemical and Biophysical Research Communications 285: 262-6.
Billi D, Caiola MG, Paolozzi L, Ghelardini P. 1998. A mathod for DNA extraction from the desert cyanobacterium Chroococcidiopsis and its application to identification of ftsZ. Applied and Environmental Microbiology 64: 4053-6.
Bogorad J. 1975. Phycobiliproteins and complimentary chromatic adaptation. Annual Review of Plant Physiology 26: 369-401.
Boulikas T. 1994. Control of DNA replication by protein phosphorylation. [Review] [63 refs]. Anticancer Research 14(6B): 2465-72.
Boussiba S, Richmond EA. 1979. Isolation and characterization of phycocyanins from the blue-green algae Spirulina platensis. Archives of Microbiology 159: 120-35.
Bradford MM. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry 72: 248-54.
Brenner PF, Mishell DR, Bernstein GS, Ortiz A. 1977. Study of medroxyprogesterone acetate and testosterone enanthate as a male contraceptive. Contraception 15: 679-91.
Bryant DA. 1982. Phycoerythrocyanin and phycoerythrin: Properties and occurrence in cyanobacteria. Journal of General Microbiology 128: 835-44.
Cain RB. 1994. Biodegradation of detergents. Current Opinion in Biotechnology 5(3): 266-74.
Chang J, Lin KH, Chen KM, Gong GC, Chiang KP. 2003. Synechococcus growth and mortality rates in the East China Sea: range of variations and correlation with environmental factors. Deep-Sea Research 50: 1265-78.
Chen HC, Chou CK, Sun CM, Yeh SF. 1997. Suppressive effects of destruxin B on Hepatitis B virus surface antigen gene expression in human hepatoma cells. Antiviral Research 34: 137-44.
Corrigan FM, Welsh SW, Skinner ER, Horrobin DF. 1994. Brain lipid in aging and in Alzheimer's disease: a review. Journal of Nutrition and Medicine 4: 327-49.
Degos F. 1999. Hepatitis C and alcohol. Journal of Hepatology 31: 113-8.
Di-Marco A, Gaetani M, Scarpinato B. 1969. Adriamycin (NSC-123,127): a new antibiotic with antitumor activity. Cancer Chemotherapy Reports 53: 33-7.
Fay P. 1992. Oxygen relations of nitrogen fixation in cyanobacteria. Microbiological Reviews 56(2): 340-73.
Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA. 1994. Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells. Molecular Pharmacology 45: 649-56.
Gantt E, Conti SF. 1965. The ultrastructure of porphyridium cruentum. The Journal of Cell Biology 26: 365-81.
Gantt E, Conti SF. 1966a. Granules associated with the chloroplast lamellae of Porphyridium cruentum. The Journal of Cell Biology 29: 423-34.
Gantt E, Conti SF. 1966b. Phycobilisome localization in algae. Brookhaven Symposium Biology 19: 393-81.
Gantt E, Lipschultz CA, Zilinskas B. 1976. Further evidence for a phycobilisome model from selective dissociation, fluorescence emission, immunoprecipitation, and electron microscopy. Biochimica et Biophysical Acta 430: 375-88.
Gerhart J, Wu M, Cyert M, Kirschner M. 1985. M-phase promoting factors from eggs of Xenopus laevis. Cytobios 43(174S): 335-47.
Glazer AN, Cohen-Bazire G. 1975. A comparision of cryptophytan phycocyanins. Archives of Microbiology 104: 29-32.
Glazer AN. 1994. Phycobiliproteins-a family of valuable, widely used fluorophores. Journal of Applied Phycology 6: 105-12.
Han R, Yang YM, Dietrich J, Luebke A, Mayer-Proschel M, Noble M. 2008. Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system. Journal of Biology 7: 12.
Hengartner MO. 2000. The biochemistry of apoptosis. Nature 407: 770-6.
Hida T, Yataba Y, Achiwa H, Muramatsu H, Kozaki K, Nakamura S, Ogawa M, Mitsudomi T, Sugiura T, Takahashi T. 1998. Increased expression of cyclooxygenase 2 occurs frequently in human lung cancers, specifically in adenocarcinomas. Cancer Research 58: 3761-4.
Huang TC, Chou WM. 1991. Setting of the circadian N2-fixing rhythm of the prokaryotic Synechococcus sp. RF-1 while its nif gene is repressed. Plant Physiology 96: 324-6.
Huang TC, Grobbelaar N. 1995. The circadian clock in the prokaryote Synechococcus RF-1. Microbiology 141: 535-40.
Huang TC, Pen SY. 1994. Induction of a circadian rhythm in Synechococcus RF-1 while the cells are in ‘‘asuspended stat’’. Planta 194: 436-8.
Huseyin M. 2000. Apoptosis: Caspases find a new place to hide. Nature 403: 29-30.
Igney FH, Krammer PH. 2002. Death and anti-death: tumour resistance to apoptosis. Nature Reviews 2: 227-88.
Jin Z, El-Deiry WS. 2005. Overview of cell death signaling pathways. Cancer Biology and Therapy 4: 139-63.
Johnson CH, Golden SS. 1999. Circadian programs in cyanobacteria: adaptiveness and mechanism. Annual Review of Microbiology 53: 389-409.
Kao ST, Yeh CC, Hsieh CC, Yang MD, Lee MR, Liu HS, Lin JG. 2001. The chinese medicine Bu-Zhong-Yi-Qi-Tang inhibited proliferation of hepatoma cell lines by inducing apoptosis via G0/G1 arrset. Life Sciences 69: 1485-96.
Kaplowits N. 2000. Mechanisms of liver cell injury. Journal of Hepatology 32: 39-47.
Katano T, Nakano S. 2006. Growth rates of Synechococcus types with different phycoerythrin composition estimated by dual-laser flow cytometry inrelationship to the light environment in the Uwa Sea. Journal of Sea Research 55: 182-90.
Kerby NW, Rowell P. 1992. Applications for photosynthetic prokaryotes. Photosynthetic Prokaryotes. Plenum Press 233-54.
Kerr JF. 1995. Neglected pooprtunities in apoptosis research. Trends in Cell Biology 5: 55-7.
Key TJ, Allen NE, Spencer EA, Travis RC. 2002. The effect of diet on risk of cancer. The Lancet 360: 861-8.
Kidd VJ. 1998. Proteolytic activities implications in tissue kinetics. Annual Review of Physiology 60: 553-73.
Kowaltowski AJ, Castilho RF, Vercesi AE. 1996. Opening of the mitochondrial permeability transition pore by uncoupling or inorganic phosphate in the presence of Ca2+ is dependent on mitochondrial generated reactive oxygen species. FEBS Letters 378: 150-2.
Krammer PH. 1999. CD95 (APO-1/Fas)-mediated apoptosis: live and let die. Advances in Immunology 71: 163-210.
Kroemer G, Petit P, Zamzami N, Vayssiere JL, Mignotte B. 1995. The biochemistry of programmed cell death. The FASEB Journal 9: 1277-87.
Kronik M, Grossman P. 1983. Immunoassay techniques with fluorescent phycobiliprotein conjugates. Clinical Chemistry 29: 1582-6.
Labianca R, Beretta G, Clerici M, Fraschini P, Luporini G. 1982. Cardiac toxicity of 5-fluorouracil: a study on 1083 patients. Tumori 68: 505-10.
Lee CC, Liu JY, Lin JK, Chu JS, Shew JY. 1998. p53 point mutation enhanced by hepatic regeneration in aflatoxin B1-induced rat liver tumors and preneoplastic lesions. Cancer Letters 125: 1-7.
Li B, Zhang X, Gao M, Chu X. 2005. Effect of CD59 on antitumoral activities of phycocyanin from Spirulina platensis. Biomedicine and Pharmacotherapy 59: 551-60.
Lissi EA, Pizarro M, Aspee A, Romay C. 2000. Kinetics of phycocyanin bilin groups destruction by peroxyl radicals. Free Radical Biology and Medicine 28: 1051-5.
Martin SJ, Reutelingsperger CPM, McGahon AJ, Rader JA, van-Schie RCAA, LaFace DM, Green DR. 1995. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. The Journal of Experimental Medicine 182(5): 1545-56.
Medema RH, Herrera RE, Lam F, Weinberg RA. 1995. Growth uppression by p16 ink4requires functional retinoblastoma protein. Proceedings of the National Academy of Sciences of the United States of America 92: 6289-93.
Megharaj M, Venkateswarlu K, Rao AS. 1989. Effects of carbofuran and carbaryl on the growth of a green alga and two cyanobacteria isolated from a rice soil. Agriculture, Ecosystems and Environment 25: 329-36.
Momparler RL, Karon M, Siegel SE, Avila F. 1976. Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells. Cancer Research 36: 2891-5.
Morschel E, Wehrmeyer W. 1975. Cryptomonad biliprotein: phycocyanin from a Chroomonas species. Archives of Microbiology 105: 153-8.
Mundt S, Kreitlow S, Nowotny A, Effmert U. 2001. Biochemical and pharmacological investigations of selected cyanobacteria. International Jouranl of Hygiene and Environmental Health 203: 327-34.
Myers CE, Young RC, Chabner BA. 1975. Biochemical determinants of 5-fluorouracil response in vivo. The Journal of Clinical Investigation 56: 1231-8.
Narro ML, Cerniglia CE, Van B, Gibson DT. 1992. Metabolism of phenanthrene by the marine cyanobacterium Agmenellum quadruplicatum PR-6. Applied and Environmental Microbiology 58 (4): 1351-9.
Oi VT, Glazer AN, Stryer L. 1982. Fluorescent phycobiliprotein conjugates for analyses of cells and molecules. The Journal of Cell Biology 93: 981-6.
Paerl HW. 1998. Structure and function of anthropogenically altered microbial communities in coastal waters. Current Opinion in Microbiology 1(3): 296-302.
Palenik B. 2001. Chromatic adaptation in marine Synechococcus strins. Applied and Environmental Microbiology 67(2): 991-4.
Pardhasaradhi BV, Ali AM, Kumari AL, Reddanna P, Khar A. 2003. Phycocyanin-mediated apoptosis in AK-5 tumor cells involves down-regulation of Bcl-2 and generation of ROS. Molecular Cancer Therapeutics 2: 1165-70.
Parrett ML, Harris RE, Joarder FS, Ross MS, Clausen KF, Robertson FM. 1997. Cyclooxygenase-2 gene expression in human breast cancer. Internationl Journal of Oncology 10: 503-7.
Patel A, Mishra S, Pawar R, Ghosh PK. 2005. Purification and characterization of C-phycocyanin from cyanobacterial species of marine and freshwater habitat. Protein Expression and Purification 40: 248-55.
Plude JL, Parker DL, Schommer OJ, Timmerman RJ, Hagstrom SA, Joers JM, Hnasko R. 1991. Chemical characterization of polysaccharide from the slime layer of the cyanobacterium Microcystis flosaquae C3-40. American Society for Microbiology 57(6): 1696-700.
Pradhan D, Krahling S, Williamson P, Schlegel RA. 1997. Multiple systems for recognition of apoptotic lymphocytes by macrophages. Molecular Biology of the Cell 8(5): 767-78.
Pru JK, Tilly JL. 2001. Programmed cell death in the ovary: insights and future prospects using genetic technologies. Molecular Endocrinology 15(6): 845-53.
Reddy CM, Bhat VB, Kiranmai G, Reddy MN, Reddanna P, Madyastha KM. 2000. Selective inhibition of cyclooxygenase-2 by C-phycocyanin, a biliprotein from Spirulina platensis. Biochemical and Biophysical Research Communications 277: 599-603.
Reddy CM, Subhashini J, Mahipal SVK, Bhat VB, Reddy PS, Kiranmai G, Madyastha KM, Reddanna P. 2003. C-Phycocyanin, a selective cyclooxygenase-2 inhibitor, induces apoptosis in lipopolysaccharide-stimulated RAW 264.7 macrophages. Biochemical and Biophysical Research Communications 304: 385-92.
Reis A, Mendes A, Lobo H, Empis JA, Novais JM. 1998. Production, extraction and purification of phycobiliproteins from Nostoc sp. Bioresource Technology 66: 181-7.
Remirez D, Fernandez V, Tapia G, Gonzalez R, Videla LA. 2002. Influence of C-phycocyanin on hepatocellular parameters related to liver oxidative stress and Kupffer cell functioning. Inflammation Research 51: 351-6.
Remirez D, Gonzalez A, Merino N, Gonzalez R, Ancheta O, Romay C, Rodriguez S. 1999. Effect of phycocyanin in zymosan-induced arthritis in mice-phycocyanin as an antiarthritis compound. Drug Development Research 48: 70-5.
Roman RB, Alvarez-Pez JM, Fernandez FGA, Grima EM. 2002. Recovery of pure B-phycoerythrin from the microalga Porphyridium cruentum. Journal of Biotechnology 93: 73-85.
Romay C, Armesto J, Remirez D, Gonzalez R, Ledon N, Garcia I. 1998a. Antioxidant and anti-inflammatory properties of C-phycocyanin from blue-green alage. Inflammation Research 47: 36-41.
Romay C, Gonzalex R, Ledon N, Remirez D, Rimbau V. 2003. Current Protein and Peptide Science 4:207-16.
Romay C, Ledón N, Gonzalez R. 1998b. Further studies on anti-inflammatory activity of phycocyanin in some animal models of inflammation. Inflammation Research 47: 334-8.
Ron D. 2002. Translational control in the endoplasmic reticulum stress response. The Journal of Clinical Investigation 110: 1383-8.
Sager R. 1992. Tumor suppressor genes in the cell cycle. [Review] [54 refs]. Current Opinion in Cell Biology 4(2): 155-60.
Sally A, Diallo MS, Castegnaro JJ, Wild CP. 1999. Interactions between hepatitis B virus infection and exposure to aflatoxins in the development of hepatocellular carcinoma: a molecular epidemiological approach. Mutation Research 428: 187-96.
Salonga D, Danenberg KD, Johnson M, Metzger R, Groshen S, Tsao-Wei DD, Lenz HJ, Leichman CG, Leichman L, Diasio RB, Danenberg PV. 2000. Colorectal tumors responding to 5-fluorouracil have low gene expression levels of dihydropyrimidine dehydrogenase, thymidylate synthase, and thymidine phosphorylase. Clinical Cancer Research 6: 1322-7.
Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M, Hla T. 1995. Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Research 55: 3785-9.
Santiago-Santos MC, Ponce-Noyola T, Olvera-Ramírez R, Ortega-López J, Cañizares-Villanueva RO. 2004. Extraction and purification of phycocyanin from Calothrix sp. Process Biochemistry 39: 2047-52.
Sarada R, Pillai MG, Ravishankar GA. 1999. Phycocyanin from spirulina sp: influence of processing of biomass on phycocyanin yield, analysis of efficacy of extraction methods and stability studies on phycocyanin. Process Biochemistry 34: 795-801.
Schlegel RA, Williamson P. 2001. Phosphatidylserine, a death knell. Cell Death and Differentiation 8(6): 551-63.
Schmitz I, Kirchhoff S, Krammer PH. 2000. Regulation of death receptormediated apoptosis pathways. The International Journal of Biochemistry and Cell Biology 32: 1123-36.
Senderowicz AM. 2004. Targeting cell cycle and apoptosis for the treatment of human malignancies. Current Opinion in Cell Biology 16: 670-8.
Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ. 1999. Ordering the cytochrome c-initiated caspase caspase: hierarchical activation of caspases-2, -3, -6, -7, -8 and -10 in a caspase-9-dependent manner. Journal of Cell Biology 144(2): 281-92.
Smith ML, Fornace AJ. 1996. Mammalian DNA damage-inducible genes associated with growth arrest and apoptosis. Mutation Research 340: 109-24.
Soni B, Kalavadia B, Trivedi U, Madamwar D. 2006. Extraction, purification and characterization of phycocyanin from Oscillatoria quadripunctulata isolated from the rocky shores of Bet-Dwarka, Gujarat, India. Process Biochemistry 41: 2017-23.
Stanley LA, Mandel HG, Riley J, Sinha S, Higginson FM, Judah DJ, Neal GE. 1999. Mutations associated with in vivo aflatoxin B1-induced carcinogenesis need not be present in the in vitro transformations by this toxin. Cancer Letters 137: 173-81.
Subhashini J, Mahipal SVK, Reddy MC, Reddy MM, Rachamallu A, Reddanna P. 2004. Molecular mechanisms in C-phycocyanin induced apoptosis in human chronic myeloid leukemia cell line-K562. Biochemical Pharmacology 68: 453-62.
Swamy SMK, Tan BKH. 2000. Cytotoxic and immunopotentiating effects of ethanolic extract of Nigella sativa L. seeds. Journal of Ethnopharmacology 70: 1-7.
Tandeau DMN, Cohen-Bazire G. 1977. Molecular composition of cyanobacterial phycobilisomes. Proceedings of the National Academy of Sciences of the United States of America 74: 1635-9.
Urashima T, Saigo K, Kobayashi S, Imaseki H, Matsubara H, Koide Y, Aseano T, Kondo Y, Koide K, Isono K. 1997. Indentification of hepatitis B virus integration in hepatitis C virus-infected hepatocelluar carcinoma tissue. Journal of Hepatology 26: 771-8.
Verhoven B, Schlegel RA, Williamson P. 1995. Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes. Cell Death and Differentiation 182(5): 1597-601.
Viskari PJ, Colyer CL. 2003. Rapid extraction of phycobiliproteins from cultured cyanobacteria samples. Analytical Biochemistry 319: 263-71.
Waterbury JB, Watson SW, Guillard RR, Brand LE. 1979. Widespread occruuence of a unicellular marine planktonic cyanobacterium. Nature 277: 293-4.
Weil M. 1996. Constitutive expression of the machinery for programmed cell death. Journal of Cell Biological 133: 1053-9.
Williams GT, Smith CA. 1993. Molecular regulation of apoptosis: genetic controls on cell death. Cell 74: 777-9.
Yoshimura R, Sano H, Masuda C, Kawamura M, Tsubouchi Y, Chargui J, Yoshimura N, Hla T, Wada S. 2000. Expression of cyclooxygenase-2 in prostate carcinoma. Cancer 89: 589-96.
Yu DY, Moon HB, Son JK, Leong S, Yu SL, Yoon H, Han YM, Lee CS, Park JS, Lee CH, Hyun BH, Murakami S, Lee KK. 1999. Incidence of hepatocelluar carcinoma in transgenic mice expressing the hepatitis B virus X-protein. Journal of Hepatology 31: 123-32.

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
系統版面圖檔 系統版面圖檔