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研究生:黃中偉
研究生(外文):Chung-Wei Huang
論文名稱:爵床素A抑制人類大腸直腸癌細胞經由粒線體相關訊息傳導路徑
論文名稱(外文):Justicidin A induces apoptosis through mitochondria dependent pathway in human colon carcinoma cell lines
指導教授:翁舷誌李政昌李政昌引用關係
指導教授(外文):Shen-Jeu WonJenq-Cang Lee
學位類別:碩士
校院名稱:國立成功大學
系所名稱:微生物及免疫學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:84
中文關鍵詞:中草藥爵床粒線體細胞凋亡大腸直腸癌
外文關鍵詞:colon cancerapoptosisJusticidin AHT-29HCT 116mitochondria
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  • 收藏至我的研究室書目清單書目收藏:1
J. procumbens 的天然抗癌成分 Justicidin A(JA),可以藉由誘導細胞凋亡而抑制人類大腸直腸癌細胞株 HT-29 及 HCT 116 的生長。隨著藥劑量的增加,以及作用的時間延長,抑制效果更佳。在HT-29 細胞中,與 JA 一起培養 6 天後,其 50% 細胞抑制濃度(IC50)為 0.11μM,而在 HCT 116 細胞則為 0.4μM,在正常人類周邊單核球細胞中,其 IC50 高達 23.0μM。此兩種細胞株在 JA 處理後,發現磷脂醯絲胺酸(phosphatidylserine)由細胞膜內面外翻至外面,sub-G1 DNA 含量增加,細胞去氧核糖核酸(DNA)有呈現梯度的斷裂的現象,顯示JA 毒殺癌細胞是經由細胞凋亡的途徑。另外也發現 JA 使細胞粒線體膜電位喪失,粒線體間區蛋白質如細胞色素c(cytochrome c)及 Smac/DIABLO 釋出到細胞質,XIAP 細胞內表現量降低,這些結果相繼促成 caspase-9 及 caspase-3 的活化。除此之外,我們也發現了抑制細胞凋亡的兩個與粒線體相關的蛋白質Bcl-2 與 Bcl-XL的量下降,而促進細胞凋亡的的蛋白質 Bax表現量則是上升。更進一步,caspase-3 的活化會切割 poly (ADP-ribose) polymerase (PARP) ,與 DNA fragmentation factor-45(DFF45)/ICAD,最終導致 DNA 的斷裂。本篇研究明確指出 J. procumbens 的萃取物 JA 可以經由誘導細胞凋亡途徑毒殺並抑制癌細胞的生長,或許 JA 與其衍生物可以成為有效而且安全的藥物,提供未來在大腸直腸癌患者治療上的幫助。
Natural antitumor agent Justicidin-A (JA), isolated from J. procumbens, induced apoptotic responses in HT-29 and HCT 116 human colorectal cancer cells in a dose- and time-dependent manner. JA inhibited the proliferation of these cancer cells and IC50 ( 50% of effective dose ) on day 6 of exposure to JA was 0.11μM for HT-29, 0.4μM for HCT 116 and 23μM for human peripheral blood mononuclear cells (PBMC). The translocation of phosphatidylserine from the inner to the outer layer of the plasma membrane, increased sub-G1 DNA contents, and fragmentation of DNA were observed in JA-treated cells. Both cells treated with JA resulted in mitochondrial perturbation including losses of mitochondrial membrane potential, releases of Smac/DIABLO and cytochrome c from mitochrondria into the cytosol, decrease the XIAP protein contents and promotes the activation of caspase-9 and caspase-3. Besides, the anti-apoptotic members of Bcl2 family, Bcl-2 and Bcl-XL, were decreased and pro-apoptotic Bax was up-regulation in JA treated cells. These may be associated with mitochondrial membrane potential which contributes to cytochrome c released from mitochondria. Furthermore, the activated caspase-3 cleavaged poly (ADP-ribose) polymerase (PARP) and DNA fragmentation factor-45(DFF45)/ICAD. All of these finially led to fragmentation of DNA. Our findings suggest that JA induces the loses of mitochondrial membrane potential, releases of Smac/DIABLO and cytochrome c from mitochondria to the cytosol, inhibits XIAP content, increases the activities of caspase-9 and –3, cleavages PARP protein and DFF45, and fragmentation of DNA. This research indicates JA may become a novel potent drug for the treatments of colorectal cancer.
目錄
頁次
中文摘要………………………………………………………1
英文摘要………………………………………………………2
致謝……………………………………………………………4
目錄……………………………………………………………5
圖表目錄………………………………………………………7
縮寫及符號……………………….…………………………..10
一、 序論
Ⅰ、大腸直腸癌發生率…………………………….………...11
Ⅱ、大腸直腸癌的致病機轉…………….…………..12
Ⅲ、細胞凋亡(Apoptosis)機制…………………………...14
Ⅳ、Justicidin A(JA)……………………………………...16
二、 材料方法
Ⅰ、細胞株…………………………………………………….17
Ⅱ、試劑……………………………………………………….17
Ⅲ、細胞生長抑制分析……………………………………….20
Ⅳ、軟洋菜膠生長分析……………………………………….20
Ⅴ、流式細胞儀分析………………………………………….21
Ⅵ、共軛焦顯微鏡照相……………………………………….24
Ⅶ、DNA斷裂分析……………………………………………24
Ⅷ、西方墨點法………………………………………………..26
三、 結果
Ⅰ、JA 對大腸直腸癌細胞及PBMC生長抑制………………30
Ⅱ、JA 誘導人類大腸直腸癌細胞凋亡……………….………30
Ⅲ、JA 誘導人類大腸直腸癌細胞凋亡路徑………………….31
Ⅳ、JA 誘導人類大腸直腸癌細胞中caspase-9 及 caspase-3 的活化…………………………………………………………32
Ⅳ、 JA 促使人類大腸直腸癌細胞粒線體間區之導致細胞凋亡因子cytochrome c 與 Smac/DIABLO釋出至細胞質……..33
Ⅴ、JA 抑制人類大腸直腸癌細胞內 XIAP蛋白質的含量…..35
Ⅵ、JA 處理使人類大腸直腸癌細胞中粒線體細胞膜電位喪失……………………………………………………………36
Ⅶ、JA 使人類大腸直腸癌細胞中粒線體上Bcl-2 成員發生變化
………………………………………………………………38
四、 討論………………………………………………………..40
五、 參考文獻…………………………………………………..45
六、 圖表………………………………………………………..54
七、 自述………………………………………………………..84

圖表目錄
頁次
Figure1. Growth inhibition of HT-29 and HCT 116 by treated with JA………………………………………………..54
Figure2. Clonogenic cell inhibition of HT-29 and HCT 116 by JA……………………………………………………..55
Figure3. Phosphatidylserine translocations in human colorectal carcinoma cells by JA………………………………..56
Figure4. Inductions of DNA fragmentation in human colorectal carcinoma cells by JA………………………………..57
Figure5. Effects of JA on sub-G1 peaks in human colorectal carcinoma cells by flow cytometry………………….58
Figure6. Effect of cycloheximide on DNA fragmentation in JA-treated HT-29 and HCT 116 cells……………….59
Figure7. Effect of Z-VAD-fmk on DNA fragmentation in JA-treated HT-29 cells……………………………….60
Figure8. Caspase-9 activation in HT-29 cells by JA………….61
Figure9. Caspase-3 activation in HT-29 cells by JA………….62
Figure10. Caspase-3 activation in HCT 116 cells by JA……...63
Figure11. Cleavage of PARP in HT-29 cells by JA……………64
Figure12. Cleavage of DFF-45 in HT-29 cells by JA………….65
Figure13. Dose dependency of release of cytochrome c from the mitochondria to cytosol in HT-29 cells by JA………66
Figure14. Dose dependency of releases of cytochrome c from the mitochondria to cytosol in HCT 116 cells by JA……………………………………………………...67
Figure15. Time course of releases of cytochrome c from the mitochondria to cytosol in HT-29 cells by JA………68
Figure16. Dose dependency of releases of Smac/DIABLO from the mitochondria to cytosol in HT-29 cells by JA……………………………………………………...69
Figure17. Dose dependency of releases of Smac/DIABLO from the mitochondria to cytosol in HCT 116 cells by JA……………………………………………………...70
Figure18. Time course of releases of Smac/DIABLO from the mitochondria to cytosol in HT-29 cells by JA………71
Figure19. Effects of JA on the expressions of XIAP in HT-29 cells…………………………………………………….72
Figure20. Effects of JA on the expressions of XIAP in HCT 116 cells…………………………………………………….73
Figure21. Changes of mitochondrial membrane potential (ΔΨm) in human colorectal carcinoma cells by JA……..74
Figure22. Changes of mitochondrial membrane potential (ΔΨm) in human colorectal carcinoma cells by JA (Confocal microscopy image )……………………….75
Figure23. Changes of mitochondrial membrane potential (ΔΨm) by confocal images analysis in human colorectal carcinoma cells by JA……………………………..76
Figure24. Effects of JA on the expressions of Bcl-2 in HT-29 cells by JA………………………………………….77
Figure25. Effects of JA on the expressions of Bcl-2 in HCT 116 cells by JA………………………………………….78
Figure26. Effects of JA on the expressions of Bcl-XL in HT-29 cells……………………………………………….79
Figure27. Effects of JA on the expressions of Bax in HT-29 cells……………………………………………….80
Figure28. Effects of JA on the expressions of Bax in HCT 116 cells……………………………………………….81
Figure29. Structure of JA…………………………………….82
Figure30. A proposed signal pathways of apoptosis induced by JA………………………………………….………...83
Tabl 1. Effect of JA response for 50% growth inhibition (IC50) and colony formation on human rectal colon HT 29, HCT 116 and PBMC……………………………………………………82
1.Astlter, V. B., and Coller, F. A. The prognostic significance of direct extension of carcinoma of the colon and rectum. Ann. Surg. 139:846. page 852, 1954.
2.American Cancer Society (ACS). Cancer facts and figures—1997. Atlanta (GA): ACS; 1997.
3.Potter, J. D. Colorectal cancer: molecules and populations. J. Natl. Cancer Inst. 91, 916-932, 1999.
4.Prior, T. W., Chadwick, R. B, Papp, A. C., Arcot, A. N., Isa, A. M., Pearl, D. K., Stemmermann, G., Percesepe, A., Loukola, A., Aaltonen, L. A., and De La Chapelle, A. The I1307K polymorphism of the APC gene in colorectal cancer. Gastroenterology, 116, 58-63, 1999.
5.Kolodner, R. D. Mismatch repair: mechanisms and relationship to cancer susceptibility. Trends. Biochem. Sci. 20, 397–401, 1995.
6.Papadopoulos, N., Nicolaides, N.C., Wei, Y.E., Ruben, S.M., Carter, K.C., Rosen, C.A., et al. Mutation of a mutL homolog in hereditary colon cancer. Science, 263, 1625–1629, 1994.
7.Mantell, L. L., Horowitz, S., Davis, J. M., and Kazzaz, J. A. Hyperoxia-induced cell death in the lung--the correlation of apoptosis, necrosis, and inflammation. Ann. N. Y. Acad. Sci. 887, 171-180, 1999.
8.Warnatz, K., Kyburz, D., Brinson, D. C., Lee, D. J., Von, D. A., Engelhart, M., Corr, M., Carson, D. A., and Tighe, H. Rheumatoid factor B cell tolerance via autonomous Fas/FasL-independent apoptosis. Cell Immunol. 191, 69-73, 1999.
9.Lynch, D. H., Campbell, K. A., Miller, R. E., Badley, A. D., and Paya, C. V. FasL/Fas and TNF/TNFR interactions in the regulation of immune responses and disease. Behring Inst. Mitt. 97, 175-184, 1996.
10.Karine, F. F., and Guido, K. Organelle-specific initiation of cell death pathways. Nature Cell Bio. 3, 255-263, 2001.
11.Jemmerson, R., LaPlante, B., and Treeful, A. Release of intact, monomeric cytochrome c from apoptotic and necrotic cells. Cell Death Differ. 9, 538-528, 2002.
12.Lorenzo, H. K., Susin, S. A., Penninger, J., and Kroemer, G. Apoptosis inducing factor (AIF): a phylogenetically old, caspase-independent effector of cell death. Cell Death Differ. 6, 516-524, 1999.
13.Zhang, X. D., Zhang, X. Y., Gray, C. P, Nguyen, T., and Hersey, P. Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of human melanoma is regulated by smac/DIABLO release from mitochondria. Cancer Res. 61, 7339-7348, 2001.
14.Cain, K., Bratton, S. B., and Cohen, G. M. The Apaf-1 apoptosome: a large caspase-activating complex. Biochimie, 84, 203-214, 2002.
15.Wang, I. K., Lin-Shiau, S. Y., and Lin, J. K. Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells. Eur. J. Cancer. 35, 1517-1525, 1999.
16.Enari, M., Sakahira, H., Yokoyama, H., Okawa, K., Iwamatsu, A., and Nagata, S. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature, 391, 43-50, 1998.
17.Watson, A. J., Askew, J.N., and Benson, R. S. Poly(adenosine diphosphate ribose) polymerase inhibition prevents necrosis induced by H2O2 but not apoptosis. Gastroenterology, 109, 472-482, 1999.
18.Casciola-Rosen, L., Nicholson, D. W., Chong, T., Rowan, K. R., Thornberry, N. A., Miller, D. K., and Rosen, A. Apopain/CPP32 cleaves proteins that are essential for cellular repair: a fundamental principle of apoptotic death. J. Exp. Med. 183, 1957-1964, 1996.
19.Reed, J. C. Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance. Curr. Opin. Oncol. 7, 541-546, 1995.
20.Oltvai, Z. N., Milliman, C. L., and Korsmeyer, S. J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell, 74, 609-619, 1993.
21.Chittenden, T., Harrington, E. A., O'Connor, R., Flemington, C., Lutz, R. J., Evan, G. I., and Guild, B. C. Induction of apoptosis by the Bcl-2 homologue Bak. Nature, 374, 733-736, 1995.
22.Yang, E., Zha, J., Jockel, J., Boise, L. H., Thompson, C.B., and Korsmeyer, S. J. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell, 80, 285-291, 1995.
23.Wang, K., Yin, X. M., Copeland, N. G., Gilbert, D. J, Jenkins, N. A, Keck, C. L, Zimonjic, D. B, Popescu, N. C, and Korsmeyer, S. J. BID, a proapoptotic BCL-2 family member, is localized to mouse chromosome 6 and human chromosome 22q11. Genomics, 53, 235-238, 1998.
24.Reed, J. C., Haldar, S., Cuddy, M. P, Croce, C., and Makover, D. Deregulated BCL2 expression enhances growth of a human B cell line. Oncogene, 4, 1123-1127, 1989.
25.Boise, L. H., Gonzalez-Garcia, M., Postema, C. E., Ding, L., Lindsten, T., Turka, L. A., Mao, X., Nunez, G., and Thompson, C. B. Bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell, 4, 597-608, 1993.
26.Gibson, L., Holmgreen, S. P., Huang, D. C., Bernard, O., Copeland, N. G., Jenkins, N. A., Sutherland, G. R., Baker, E., Adams, J. M., and Cory, S. Bcl-w, a novel member of the bcl-2 family, promotes cell survival. Oncogene, 13, 665-675,1996.
27.Kroemer, G., and Reed, J. C. Mitochondrial control of cell death. Nature Med. 6, 513–519, 2000.
28.Zamzami, N., and Kroemer, G. Mitochondria in apoptosis. How Pandora’s box opens. Nature Rev. Mol. Cell Biol. 2, 67–71, 2001.
29.Zamzami, N, Marchetti, P., Castedo, M., Hirsch, T., Susin, S. A., Masse, B., and Kroemer, G. Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis. FEBS Lett. 384, 53–57, 1996.
30.Szabo, I., and Zoratti, M. The mitochondrial megachannel is the permeability transition pore. J. Bioenerg. Biomembr. 24, 111-117, 1992.
31.Martin, H. and Robert, G. K. XIAP, the guardian angel Nature Rev. 2, 550-556, 2001.
32.Ekert, P. G., Silke, J. and Vaux, D. L. Caspase inhibitors. Cell Death Differ. 6, 1081–1086, 1999.
33.Du, C., Fang, M., Li, Y., Li, L. and Wang, X. Smac, a mitochondrial protein that promotes cytochrome c dependent caspase activation by eliminating IAP inhibition. Cell, 102, 33–42, 2000.
34.Verhagen, A. M., Ekert, P. G., Pakusch, M., Silke, J., Connolly, L. M., Reid, G. E., Moritz, R. L., Simpson, R. J., and Vaux, D. L. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell, 102, 43–53, 2000.
35.Gu, J., Dong, R. P., Zhang, C., McLaughlin, D. F., Wu, M. X., and Schlossman, S. F. Functional interaction of DFF35 and DFF45 with caspase-activated DNA fragmentation nuclease DFF40. J. Biol. Chem. 274, 20759-20762, 1999.
36.JunAsano, Kazuhiro, C., Masahiro, T., Takao, Y. Antiviral activity of ligans and their glycosides from Justicia Procumbens. Phytochemistry, 3, 713-717, 1996.
37.Day, S. H., Chiu, N. Y., Won, S. J., and Lin C.N. J. Natl. Prod. Cytotoxic lignans of Justicia ciliata. 62, 1056-1058, 1999.
38.Francesc, X. S., Cecýlia, G., Jaume, C., Merce, P., Elena, E., Jorge, C., and Antonio, C. Evaluation of free radical production, mitochondrial membrane potential and cytoplasmic calcium in mammalian neurons by flow cytometry. Brain Res. Prot. 4, 280–287, 1999.
39.Anthony, M., Ying, H., Barbara, K., Kemp, Alberto, A. B., and Jorge D. E. Evaluation of fluorescent dyes for the detection of mitochondrial membrane potential changes in cultured cardiomyocytes. Card. Res. 46, 126–138, 2000.
40.Chandra, R., Joshi, P. C., Bajpai, V. K., and Gupta, C. M. Membrane phospholipid organization in calcium-loaded human erythrocytes. Biochim. Biophys. Acta. 902, 253-262, 1987.
41.Tait, J. F., and Gibson, D. Phospholipid binding of annexin V: effects of calcium and membrane phosphatidylserine content. Arch. Biochem. Biophys. 298, 187-191, 1992.
42.Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., Alnemri, E. S., and Wang, X. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell, 91,479-489, 1997.
43.Stehlik, C., Martin, R., Kumabashiri, I., Schmid, J. A., Binder, B. R., and Lipp, J. Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J. Exp. Med. 188, 211-216, 1998.
44.Liu, Z., Sun, C., Olejniczak, E. T., Meadows, R. P., Betz, S. F., Oost, T., Herrmann, J., Wu, J. C., and Fesik, S. W. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature, 408, 1004-1008, 2000.
45.Suzuki, Y., Nakabayashi, Y., Nakata, K., Reed, J. C., and Takahashi, R. X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and -7 in distinct modes. J. Biol. Chem. 276, 27058-27053, 2001.
46.Takahashi, R., Deveraux, Q., Tamm, I., Welsh, K., Assa, M. N., Salvesen, G. S., and Reed, J.C. A single BIR domain of XIAP sufficient for inhibiting caspases. J. Biol. Chem. 273, 7787-7790, 1998.
47.Juan, G., Cavazzoni, M., Saez, G. T., and O'Connor, J. E. A fast kinetic method for assessing mitochondrial membrane potential in isolated hepatocytes with rhodamine 123 and flow cytometry. Cytometry, 15, 335-342, 1994.
48.Martinou, J. C. Apoptosis. Key to the mitochondrial gate. Nature, 399, 411-412, 1999.
49.Yang, J., Liu, X., Bhalla, K., Kim, C. N., Ibrado, A. M., Cai, J., Peng, T. I., Jones, D. P., and Wang, X. D. Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked. Science, 275, 1129-1132, 1997.
50.Kobayashi, T., Sawa, H., Morikawa, J., Zhang, W., and Shiku, H. Bax induction activates apoptotic cascade via mitochondrial cytochrome c release and Bax overexpression enhances apoptosis induced by chemotherapeutic agents in DLD-1 colon cancer cells. J. Cancer Res. 91, 1264-1268, 2000.
51.Lenaz, G., Bovina, C., D'Aurelio, M., Fato, R., Formiggini, G., Genova, M. L., Giuliano, G., Pich, M. M., Paolucci, U., Castelli, G. P., and Ventura, B. Role of mitochondria in oxidative stress and aging. Ann. N. Y. Acad. Sci. 959, 199-213, 2002.
52.Taneja, N., Tjalkens, R., Philbert, M. A., and Rehemtulla, A. Irradiation of mitochondria initiates apoptosis in a cell free system. Oncogene, 20, 167-177, 2001.
53.Ferreira, C. G., Span, S.W., Peters, G. J., Kruyt, F.A., and Giaccone, G. Chemotherapy triggers apoptosis in a caspase-8-dependent and mitochondria-controlled manner in the non-small cell lung cancer cell line NCI-H460.Cancer Res. 60, 7133-7141, 2000.
54.Vayssier, T. M., Kreps, S. E., Adrie, C., Dall'Ava, J., Christiani, D., and Polla, B. S. Mitochondrial membrane potential: a novel biomarker of oxidative environmental stress. Environ. Health. Perspect. 110, 301-305, 2002.
55.Luo, D., Cheng, S. C., and Xie, Y. Expression of Bcl-2 family proteins during chemotherapeutic agents-induced apoptosis in the hepatoblastoma HepG2 cell line. Br. J. Biomed. Sci. 56,114-122, 1999.
56.Laurence, G. P., Pengfei, L., Solange, L., Georges, C., Marie-Ange, D., Sylvie, C., Nicole, G., Jacques, T., and François, T. Sulforaphane, a Naturally Occurring Isothiocyanate, Induces Cell Cycle Arrest and Apoptosis in HT29 Human Colon Cancer Cells. Cancer Res. 60, Cancer Res. 2000 60: 1426-1433, 2000.
57.Papas, S., Crepel, V., Hasboun, D., Jorquera, I., Chinestra, P., and Ben-Ari, Y. Cycloheximide Reduces the Effects of Anoxic Insult In Vivo and In Vitro. Eur. J. Neurosci. 4, 758-765, 1992.
58.Tang, G., Minemoto, Y., Dibling, B., Purcell, N. H., Li, Z., Karin, M., and Lin, A. Inhibition of JNK activation through NF-kappaB target genes. Nature, 414, 313-317, 2001.
59.Tamm, I., Kornblau, S.M., Segall, H., Krajewski, S., Welsh, K., Kitada, S., Scudiero, D. A., Tudor, G., Qui, Y. H., Monks, A., Andreeff, M., and Reed, J. C. Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin. Cancer Res. 6, 1796-1803, 2000.
60.Kleeff, J., Kornmann, M., Sawhney, H., and Korc, M. Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells. Int. J. Cancer. 86, 399-407, 2000.
61.Kleeff, J., Kornmann, M., Sawhney, H., and Korc, M. Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells. Int. J. Cancer. 86, 399-407, 2000.
62.Slee, E. A., Zhu, H., Chow, S. C., MacFarlane, M., Nicholson, D.W., and Cohen, G. M. Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32. Biochem. J. 315, 21-24, 1996.
63.Kim, M. J., Jo, D. G, Hong, G. S., Kim, B. J., Lai, M., Cho, D.H., Kim, K. W., Bandyopadhyay, A., Hong, Y. M., Kim, D. H, Cho, C., Liu, J. O., Snyder, S. H., and Jung, Y. K. Calpain-dependent cleavage of cain/cabin1 activates calcineurin to mediate calcium-triggered cell death. Proc. Natl. Acad. Sci. 99, 9870-9875, 2002.
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