臺灣博碩士論文加值系統

本實驗以嘉義東石的文蛤Meretrix lusoria (Hard Clam；HC) 直接以乙酸乙酯進行分層萃取(HC-EA)為實驗材料，進行細胞凋亡機制研究。初步結果發現HC-EA對人類血癌HL-60細胞生長有抑制作用，但對人類正常多形性單核白血球細胞PMNs則無細胞毒性。由DNA電泳分析發現，處理HC-EA會造成人類血癌 (HL-60)細胞DNA的片斷化，造成細胞內染色質凝集與磷脂質外翻；在細胞流式儀(flow cytometry)的實驗顯示HC-EA促使HL-60細胞的Sub G1上升，並且與濃度(dose dependent)及時間(time dependent)呈相關性。HC-EA誘導HL-60細胞內ROS的產生、GSH的表現量下降及細胞粒線體膜電位(ΔΨm)下降。此外，我們亦使用抗氧化劑如allopurinol (ALL)、catalase (CAT)、 diphenylene iodonium(DPI) 、 N-acetylcysteine (NAC)、 pyrrolidine dithiocarbamate (PDTC) 和superoxide dismutase (SOD)來探討ROS的產生對細胞凋亡(apoptosis)的影響，結果發現catalase、 NAC、PDTC和SOD可抑制HC-EA所造成的細胞凋亡。西方墨點法的實驗結果亦顯示HC-EA會造成Mcl-1、DFF-45及Bid蛋白質表現量下降。由caspase活性分析的結果顯示HC-EA會促使caspase-2及-3的活性上升，但處理caspase的總抑制劑（Z-VAD-FMK），則可抑制HC-EA所造成的細胞凋亡產生。故經由以上的實驗結果我們推測HC-EA造成人類血癌細胞株(HL-60 cells)的凋亡，可能經由自由基的產生而使得粒線體的膜電位下降，cytochrome c釋放至cytosol後，活化caspase-9及caspase-3，最後因DFF-45降解使得CDA (caspase-activated deoxyribonuclease)進入細胞核內，而造成DNA的片斷化。至於文蛤的真正活性物質經純化後得到一有效化合物epidioxysterols (EDS)，包含5α,8α-epidioxy-24(R)-methylcholest-6-en-3β-ol 及5α,8α-epidioxy-24(S)-methylcholest-6-en-3β-ol兩種sterol，經實驗證實epidioxysterols (EDS) 能更有效的誘導HL-60細胞凋亡，且具有抗發炎之功效。故建議EDS可作為文蛤未來開發成保健食品之依據。

The apoptosis-induced fractionation and purification was used to identify the bioactive components of Hard clams (HC), Meretrix lusoria. The effects of ethyl acetate extract of HC (HC-EA) on cell viability in human cancer cells were investigated. Dissipation of mitochondrial membrane potential, release of mitochondrial cytochrome c into cytosol and subsequent induction of pro-caspase-9 and -3 processing preceded confirmation of induction of apoptosis in HL-60 cells by DNA fragmentation, chromatin condensation, changes in the cell membrane and the appearance of a sub-G1 DNA peak. Furthermore, treatment with HC-EA caused a rapid loss of intracellular glutathione content and stimulation of reactive oxygen species (ROS). Antioxidants such as catalase, N-acetylcysteine, pyrrolidine dithiocarbamate, and superoxide dismutase, but not allopurinol and diphenylene iodonium, significantly inhibited HC-EA-induced cell death. Apoptosis was completely prevented by a pan-caspase inhibitor, z-Val-Ala-Asp-fluoromethyl ketone (z-VAD-FMK). The ethyl acetate fraction was then subjected to separation and purification using silica gel column chromatography. The compounds showing strong apoptosis inducing activity were identified by spectral methods as: 5α,8α-epidioxy-24(S)-methylcholest-6-en-3β-ol and 5α,8α- epidioxy-24(R) -methylcholest-6-en-3β-ol.

Part 1：Hard Clam (Meretrix lusoria)
中文摘要 (文蛤)------------------------------------------------------02
Abstract (Meretrix lusoria)----------------------------------------04
第壹章 緒論----------------------------------------------------------05
第貳章 文獻整理------------------------------------------------------07
第一節、文蛤的介紹----------------------------------------------------07
第二節、血癌的介紹----------------------------------------------------09
第三節、細胞凋亡-----------------------------------------------------12
(一)細胞凋亡特徵-----------------------------------------------------13
(二)凋亡機制---------------------------------------------------------16
(三)細胞凋亡路徑-----------------------------------------------------17
(1)死亡接受器途徑(Death receptor pathway)--------------------------17
(2)粒腺體途徑(Mitochondrial pathway)---------------------------------19
(3)內質網壓力途徑(Endoplasmic reticulum stress pathway) --------20
(四)Bcl-2 family蛋白質----------------------------------------------22
(五)Caspase蛋白酶---------------------------------------------------24
第四節、ROS( Reactive Oxygen Species)與細胞凋亡之關係-------------27
第參章 材料與方法----------------------------------------------------29
第肆章 結果與討論----------------------------------------------------54
第伍章 討論----------------------------------------------------------68

Part 2：Oyster (Crassotreas gigas)
中文摘要 (牡蠣)------------------------------------------------------90
Abstract (Crassotreas gigas)---------------------------------------91
第壹章 緒論----------------------------------------------------------92
第貳章 文獻整理------------------------------------------------------94
第參章 材料與方法----------------------------------------------------95
第肆章 結果與討論----------------------------------------------------99
第伍章 討論---------------------------------------------------------109
參考文獻----------------------------------------------------------127

參考文獻
何雲達，1995。台灣農家要覽漁業篇。豐年社。台北。台灣。p.252。
何雲達，1996。台灣農業要覽漁業篇。行政院農委會。台北。台灣。pp.245-255。
吳玉茹，2004。 長牡蠣殼內珍珠層之水溶性萃取物對造骨細胞的影響。中山醫學大學碩士論文。
辛宜鴻，2005。研究Dibenzoylmethane類似物對皮膚的化學預防機制。國立高雄海洋科技大學水產食品科學系碩士論文。
林岳暉，1996。以無血清培養模式研究文蛤萃取液對細胞性免疫力之影響。國立台灣海洋大學水產食品科學系碩士論文。
林瑩禎，1999。我國保健食品市場現況與趨勢。食品市場資訊，88(12) : 1-3。
林子青，2004。貝類熱水抽出物與水解物中胜肽對血管升壓素轉換酶之抑制與其純化。國立台灣海洋大學食品科學系碩士論文。
金宗濂、文鏡、唐粉芳和陳文，1995。功能性食品評價原理和方法。北京大學出版社，pp.67-85
陳聰松，1999。介紹幾種水產品的特殊機能。潮訊。109: 4-11。
陳佳伶，2005。文蛤水解物中胜肽對血管升壓素轉換酶之抑制與其純化。國立台灣海洋大學食品科學系碩士論文。
程金燕，2000。由改善腸胃道的功能來探討機能性食品的功效。食品工業，32(6) : 48-56。
黄巧淇，2001。文蛤熱水萃取物醣蛋白之細胞凋亡誘導機制。國立台灣海洋大學食品科學系碩士論文。
黃怡璇，2005。研究蜆萃取物(FME)誘發人類血癌細胞凋亡之機制。國立高雄海洋科技大學水產食品科學系碩士論文。
楊鴻嘉和丁雲源。1984。文蛤人工繁殖之研究。台灣省水產試驗所試驗報告，36: 98-111。
漁業署，2004。中華民國台灣地區漁業年報。
劉怡青，2004。文蛤抽出物之抗氧化活性與其季節及產地之變動。國立台灣海洋大學食品科學系碩士論文。
潘敏雄，1995。文蛤萃取物抗人體肝癌細胞因子的純化與特性研究。國立台灣海洋大學水產食品研究所碩士論文。
賴呈委，2000。文蛤凝集素樣成分之腫瘤細胞凋亡調節作用。國立台灣海洋大學食品科學系碩士論文。
賴慶紓，2005。Acacetin抗發炎與引發人類胃癌細胞凋亡機制之探討。國立高雄海洋科技大學水產食品科學系碩士論文。
蕭泉源、陳莉臻、林瑞堂。2001。泡水處理對牡蠣化學成分與品質之影
響。台灣農化與食品科學。39:122-128。
References

Adams, J. M. and Cory, S. (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281: 1322-1326.
Allen, R. T., Cluck, M. W., and Agrawal, D. K. (1998) Mechanisms controlling cellular suicide: role of Bcl-2 and caspases. Cell Mol Life Sci 54: 427-445.
Ashkenazi, A. and Dixit, V. M. (1998) Death receptors: signaling and modulation. Science 281: 1305-1308.
Atif B. A. and Carol S. F. (2000) Phytosterols as anticancer dietary components: evidence and mechanism of action. J Nutr 130:2127-2130.
Balaban, R. S., Nemoto, S., and Finkel, T. (2005) Mitochondria, oxidants, and aging. Cell 120: 483-495.
Barnes, S. (1994) Biochemical targets of the isoflavone genistein in tumor cell lines. Proc Soc Exp Med Biol 208: 103-108.
Barnes, S. (1995) Effect of genistein on in vitro and in vivo models of cancer. J Nutr 125: 777S-783S.
Barnhart, B. C., Alappat, E. C., and Peter, M. E. (2003) The CD95 type I/type II model. Semin Immunol 15: 185-193.
Boatright, K. M. and Salvesen, G. S. (2003) Mechanisms of caspase activation. Curr Opin Cell Biol 15: 725-731.
Castaigne, S., Chomienne, C., Daniel, M. T., Ballerini, P., Berger, R., Fenaux, P., Degos, L. (1990) All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results. Blood 76: 1704-1709.
Chen, G. Q., Zhu, J., Shi, X. G., Ni, J. H., Zhong, H. J., Si, G. Y., Jin, X. L., Tang, W., Li, X. S., Xong, S. M., Shen, Z. X., Sun, G. L., Ma, J., Zhang, P., Zhang, T. D., Gazin, C., Naoe, T., Chen, S. J., Wang, Z. Y., Chen, Z. (1996) In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 88: 1052-1061.
Chereau, D., Zou, H., Spada, A. P., and Wu, J. C. (2005) A nucleotide binding site in caspase-9 regulates apoptosome activation. Biochemistry 44: 4971-4976.
Chiou, T. K., Lin, J. F. and Shiau, C. Y. (1996) Seasonal variation in chemical components of cultured hard clams ( Meretrix lusoria ). Food Sci 23: 779-787.
Chisari, F. V., Filippi, P., McLachlan, A., Milich, D. R., Riggs, M., Lee, S., Palmiter, R. D., Pinkert, C. A., Brinster, R. L. (1986) Expression of hepatitis B virus large envelope polypeptide inhibits hepatitis B surface antigen secretion in transgenic mice. J Virol 60: 880-887.
Chomienne, C., Ballerini, P., Balitrand, N., Daniel, M. T., Fenaux, P., Castaigne, S., Degos, L. (1990) All-trans retinoic acid in acute promyelocytic leukemias. II. In vitro studies: structure-function relationship. Blood 76: 1710-1717.
Chou, J. J., Li, H., Salvesen, G. S., Yuan, J., and Wagner, G. (1999) Solution structure of BID, an intracellular amplifier of apoptotic signaling. Cell 96: 615-624.
Chun, K. S. and Surh, Y. J. (2004) Signal transduction pathways regulating cyclooxygenase-2 expression: potential molecular targets for chemoprevention. Biochem Pharmacol 68: 1089-1100.
Danial, N. N. and Korsmeyer, S. J. (2004) Cell death: critical control points. Cell 116: 205-219.
Datta, S. R., Katsov, A., Hu, L., Petros, A., Fesik, S. W., Yaffe, M. B., Greenberg, M. E. (2000) 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell 6: 41-51.
Diaz, J. L., Oltersdorf, T., Horne, W., McConnell, M., Wilson, G., Weeks, S., Garcia, T., Fritz, L. C. (1997) A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members. J Biol Chem 272: 11350-11355.
Dotto, G. P. (2000) p21(WAF1/Cip1): more than a break to the cell cycle? Biochim Biophys Acta 1471: M43-M56.
Edinger, A. L. and Thompson, C. B. (2004) Death by design: apoptosis, necrosis and autophagy. Curr Opin Cell Biol 16: 663-669.
Enari, M., Talanian, R. V., Wong, W. W., and Nagata, S. (1996) Sequential activation of ICE-like and CPP32-like proteases during Fas-mediated apoptosis. Nature 380: 723-726.
Fargion, S., Fracanzani, A. L., Piperno, A., Braga, M., D'Alba, R., Ronchi, G., Fiorelli, G. (1994) Prognostic factors for hepatocellular carcinoma in genetic hemochromatosis. Hepatology 20: 1426-1431.
Gallagher, R. E. and Gallo, R. C. (1975) Type C RNA tumor virus isolated from cultured human acute myelogenous leukemia cells. Science 187: 350-353.
Gonzalvez, F., Pariselli, F., Dupaigne, P., Budihardjo, I., Lutter, M., Antonsson, B., Diolez, P., Manon, S., Martinou, J. C., Goubern, M., Wang, X., Bernard, S., Petit, P. X. (2005) tBid interaction with cardiolipin primarily orchestrates mitochondrial dysfunctions and subsequently activates Bax and Bak. Cell Death Differ 12: 614-626.
Goodlett, C. R. and Horn, K. H. (2001) Mechanisms of alcohol-induced damage to the developing nervous system. Alcohol Research & Health 25: 175-184.
Gouaze, V., ndrieu-Abadie, N., Cuvillier, O., Malagarie-Cazenave, S., Frisach, M. F., Mirault, M. E., Levade, T. (2002) Glutathione peroxidase-1 protects from CD95-induced apoptosis. J Biol Chem 277: 42867-42874.
Grace, P. A. (1994) Ischaemia-reperfusion injury. Br J Surg 81: 637-647.
Gralnick, H. R. and Sultan, C. (1975) Acute promyelocytic leukaemia: haemorrhagic manifestation and morphologic criteria. Br J Haematol 29: 373-376.
Hengartner, M. O. (2000) The biochemistry of apoptosis. Nature 407: 770-776.
Hengartner, M. O., Ellis, R. E., and Horvitz, H. R. (1992) Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 356: 494-499.
Hengartner, M. O. and Horvitz, H. R. (1994) C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell 76: 665-676.
Huseyin M. (2000) Apoptosis: Caspases find a new place to hide. Nature 403: 29-30.
Idriss, H. T. and Naismith, J. H. (2000) TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech 50: 184-195.
Ikuko, O. (1992) Structure and properties of Ptilomycalin A. J Am Chem Soc 114: 8472-8479.
Jerry M.A. and Suzanne C. (1998) The Bcl-2 Protein Family: Arbiters of Cell Survival. SCIENCE 281: 1322-1326.
Jin, Z. and El-Deiry, W. S. (2005) Overview of cell death signaling pathways. Cancer Biol Ther 4: 139-163.
Jin, Z., Gao, F., Flagg, T., and Deng, X. (2004) Nicotine induces multi-site phosphorylation of Bad in association with suppression of apoptosis. J Biol Chem 279: 23837-23844.
Jordan, C. T. (2004) Cancer stem cell biology: from leukemia to solid tumors. Curr Opin Cell Biol 16: 708-712.
Kantarjian, H. M., Keating, M. J., Walters, R. S., Estey, E. H., McCredie, K. B., Smith, T. L., Dalton, W. T., Jr., Cork, A., Trujillo, J. M., Freireich, E. J. (1986) Acute promyelocytic leukemia. M.D. Anderson Hospital experience. Am J Med 80: 789-797.
Katayose, Y., Kim, M., Rakkar, A. N., Li, Z., Cowan, K. H., and Seth, P. (1997) Promoting apoptosis: a novel activity associated with the cyclin-dependent kinase inhibitor p27. Cancer Res 57: 5441-5445.
Kelekar, A., Chang, B. S., Harlan, J. E., Fesik, S. W., and Thompson, C. B. (1997) Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL. Mol Cell Biol 17: 7040-7046.
Kelekar, A. and Thompson, C. B. (1998) Bcl-2-family proteins: the role of the BH3 domain in apoptosis. Trends Cell Biol 8: 324-330.
Kerr, J. F. (2002) History of the events leading to the formulation of the apoptosis concept. Toxicology 181-182: 471-474.
Kerr, J. F., Winterford, C. M., and Harmon, B. V. (1994) Apoptosis. Its significance in cancer and cancer therapy. Cancer 73: 2013-2026.
Kerr, J. F., Wyllie, A. H., and Currie, A. R. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26: 239-257.
Kong, Z. L., Chiang, L. C., Fang, F., Shinohara, K., and Pan, P. (1997) Immune bioactivity in shellfish toward serum-free cultured human cell lines. Biosci Biotechnol Biochem 61: 24-28.
Korsmeyer, S. J. (1992) Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood 80: 879-886.
Kroemer, G., Dallaporta, B., and Resche-Rigon, M. (1998) The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Physiol 60: 619-642.
Lee, T. G. and Maruyama, S. (1998) Isolation of HIV-1 protease-inhibiting peptide from thermolysin hydrolysate of oyster proteins. Biochemical andBiophysical Research Communications 253: 604-608.
Liu, X., Zou, H., Slaughter, C., and Wang, X. (1997) DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 89: 175-184.
Loignon M., Fetni R., Gordon A.J., and Drobetsky E.A. (1997) A p53-independent pathway for induction of p21Cip/WAF and concomitant G1 arrest in VV-irradiated human skin fibroblast. Cancer Rea 57: 3390-3394.
Los, M., Burek, C. J., Stroh, C., Benedyk, K., Hug, H., and Mackiewicz, A. (2003) Anticancer drugs of tomorrow: apoptotic pathways as targets for drug design. Drug Discov Today 8: 67-77.
Lutter, M., Perkins, G. A., and Wang, X. (2001) The pro-apoptotic Bcl-2 family member tBid localizes to mitochondrial contact sites. BMC Cell Biol 2: 22.
Marletta, M. A. (1989) Nitric oxide: biosynthesis and biological significance. Trends Biochem Sci 14: 488-492.
Mayer, B. and Oberbauer, R. (2003) Mitochondrial regulation of apoptosis. News Physiol Sci 18: 89-94.
McCann, J. and Ames, B. N. (1976) Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. Proc Natl Acad Sci U S A 73: 950-954.
Midgley, C. A., Owens, B., Briscoe, C. V., Thomas, D. B., Lane, D. P., and Hall, P. A. (1995) Coupling between gamma irradiation, p53 induction and the apoptotic response depends upon cell type in vivo. J Cell Sci 108 ( Pt 5): 1843-1848.
Miura, M., Zhu, H., Rotello, R., Hartwieg, E. A., and Yuan, J. (1993) Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 75: 653-660.
Mukhopadhyay, A., Bueso-Ramos, C., Chatterjee, D., Pantazis, P., and Aggarwal, B. B. (2001) Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene 20: 7597-7609.
Oltvai, Z. N., Milliman, C. L., and Korsmeyer, S. J. (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609-619.
Pan M.H. (2000) Induction of apoptosis by the oolong tea polyphenol theasinesin a through cytochrome c release and activation of caspases-9 and caspases-3 in Human U937 cells. J Agric Food Chem 48: 6337-6346.
Phillips, T. J., Salman, S. M., Bhawan, J., and Rogers, G. S. (1998) Burn scar carcinoma. Diagnosis and management. Dermatol Surg 24: 561-565.
Rathmell, J. C. and Thompson, C. B. (2002) Pathways of apoptosis in lymphocyte development, homeostasis, and disease. Cell 109 Suppl: S97-107.
Reed, J. C. (1994) Bcl-2 and the regulation of programmed cell death. J Cell Biol 124: 1-6.
Reed, J. C. (1998) Bcl-2 family proteins. Oncogene 17: 3225-3236.
Riedl, S. J., Li, W., Chao, Y., Schwarzenbacher, R., and Shi, Y. (2005) Structure of the apoptotic protease-activating factor 1 bound to ADP. Nature 434: 926-933.
Rivedal, E. and Witz, G. (2005) Benzene metabolites block gap junction intercellular communication. Role in hematotoxicity and leukemia? Chem Biol Interact 153-154: 257-260.
Ron, D. (2002) Translational control in the endoplasmic reticulum stress response. J Clin Invest 110: 1383-1388.
Saelens, X., Festjens, N., Vande, W. L., van, G. M., van, L. G., and Vandenabeele, P. (2004) Toxic proteins released from mitochondria in cell death. Oncogene 23: 2861-2874.
Sakahira, H., Enari, M., and Nagata, S. (1998) Cleavage of CAD inhibitor in CAD activation and DNA degradation during apoptosis. Nature 391: 96-99.
Sheu, J. H., Chang, K. C., and Duh, C. Y. (2000) A cytotoxic 5alpha,8alpha-epidioxysterol from a soft coral Sinularia species. J Nat Prod 63: 149-151.
Shi, Y. (2002) Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell 9: 459-470.
Slamon, D. J., Shimotohno, K., Cline, M. J., Golde, D. W., and Chen, I. S. (1984) Identification of the putative transforming protein of the human T-cell leukemia viruses HTLV-I and HTLV-II. Science 226: 61-65.
Somasundaram, S., Edmund, N. A., Moore, D. T., Small, G. W., Shi, Y. Y., and Orlowski, R. Z. (2002) Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res 62: 3868-3875.
Takei, T., Yoshida, M., Ohnishi-Kameyama, M., and Kobori, M. (2005) Ergosterol peroxide, an apoptosis-inducing component isolated from Sarcodon aspratus (Berk.) S. Ito. Biosci Biotechnol Biochem 69: 212-215.
Tanaka, T., Makita, H., Kawabata, K., Mori, H., Kakumoto, M., Satoh, K., Hara, A., Sumida, T., Tanaka, T., Ogawa, H. (1997) Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin. Carcinogenesis 18: 957-965.
Varfolomeev, E. E., Schuchmann, M., Luria, V., Chiannilkulchai, N., Beckmann, J. S., Mett, I. L., Rebrikov, D., Brodianski, V. M., Kemper, O. C., Kollet, O., Lapidot, T., Soffer, D., Sobe, T., Avraham, K. B., Goncharov, T., Holtmann, H., Lonai, P., Wallach, D. (1998) Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity 9: 267-276.
Veis, D. J., Sentman, C. L., Bach, E. A., and Korsmeyer, S. J. (1993) Expression of the Bcl-2 protein in murine and human thymocytes and in peripheral T lymphocytes. J Immunol 151: 2546-2554.
Warner, D. S., Sheng, H., and Batinic-Haberle, I. (2004) Oxidants, antioxidants and the ischemic brain. J Exp Biol 207: 3221-3231.
Weber, C. H. and Vincenz, C. (2001) A docking model of key components of the DISC complex: death domain superfamily interactions redefined. FEBS Lett 492: 171-176.
Wilkinson, J. C., Wilkinson, A. S., Scott, F. L., Csomos, R. A., Salvesen, G. S., and Duckett, C. S. (2004) Neutralization of Smac/Diablo by inhibitors of apoptosis (IAPs). A caspase-independent mechanism for apoptotic inhibition. J Biol Chem 279: 51082-51090.
Williams, C. S., Mann, M., and DuBois, R. N. (1999) The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18: 7908-7916.
Wu, T. H., Yang, R. L., Xie, L. P., Wang, H. Z., Chen, L., Zhang, S., Zhao, Y., Zhang, R. Q. (2006) Inhibition of cell growth and induction of G1-phase cell cycle arrest in hepatoma cells by steroid extract from Meretrix meretrix. Cancer Lett 232: 199-205.
Wyllie, A. H. (1997) Apoptosis: an overview. Br Med Bull 53: 451-465.
Wynder, E. L. and Gori, G. B. (1977) Contribution of the environment to cancer incidence: an epidemiologic exercise. J Natl Cancer Inst 58: 825-832.
Xu, C., Bailly-Maitre, B., and Reed, J. C. (2005) Endoplasmic reticulum stress: cell life and death decisions. J Clin Invest 115: 2656-2664.
Yin, X. M., Oltvai, Z. N., and Korsmeyer, S. J. (1994) BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature 369: 321-323.