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研究生:郭峻良
研究生(外文):Jun-Liang Kuo
論文名稱:去氫齒孔酸及其衍生物導致神經膠原瘤細胞死亡的作用機轉
論文名稱(外文):Mechanisms Underlying Dehydroeburicoic Acid Derivatives-induced Cell Death in U87MG Glioblastoma Cells
指導教授:鄭瓊娟
指導教授(外文):Chung-Jiuan Jeng
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:解剖學及細胞生物學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:67
中文關鍵詞:牛樟芝神經膠原瘤細胞去氫齒孔酸細胞週期細胞壞死細胞凋亡
外文關鍵詞:Antrodia cinnamomeaglioblastomadehydroeburicoic acidcell cyclenecrosisapoptosis
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許多的研究報告指出三萜類化合物具有抗癌藥性,本實驗室先前已經證實台灣特有蕈菇類植物牛樟芝的重要化學成份之一: 三萜類化合物-去氫齒孔酸(Dehydroeburicoic acid, DeEA),會造成神經膠原瘤細胞U87MG大量消耗ATP、細胞內鈣離子濃度增加、活化calpain,而引發細胞壞死(necrosis)。因此,本論文的主要目的是要進一步地探討DeEA造成U87MG細胞壞死路徑的分子機制,並同時研究DeEA的兩種衍生物:21號碳添加甲基的Methyl Dehydroeburicoate (M-DeEA),以及3號碳加乙酸酯基的Dehydroeburicoic acid monoacetate (MA-DeEA), 對神經膠原瘤細胞生長的影響。
神經膠原瘤細胞在經過三種藥物處理24小時後,細胞存活率和細胞毒性分析結果顯示DeEA、M-DeEA和MA-DeEA皆會抑制細胞的生長能力。在光學顯微鏡下觀察細胞的形態變化,發現三種藥物造成神經膠原瘤細胞不同的形態變化:DeEA造成細胞縮短呈現球狀而且破裂,M-DeEA處理的細胞也有呈現縮短但是沒有明顯細胞破裂, MA-DeEA則造成細胞呈現不規則細長形態或呈圓形漂浮的狀態。因此,我們進一步分析比較這三種藥物對U87MG 細胞生長抑制與死亡機制的差異。
藥物處理後的細胞以Annexin V/propidium iodide (PI)染色,再以流式細胞儀分析細胞死亡形式,結果顯示DeEA會造成U87MG細胞壞死,M-DeEA和MA-DeEA則是傾向增加細胞的凋亡。以AO/ EtBr染色分析細胞死亡形式,也顯示M-DeEA會增加細胞凋亡的比例。但當細胞以抑制細胞凋亡的蛋白酵素抑制劑先處理以抑制細胞凋亡,並不能明顯抑制MA-DeEA造成的細胞死亡。此外,以PI染色分析細胞週期變化時則發現MA-DeEA會促進細胞停留在G2/M期。
以免疫螢光染色偵測自噬體膜蛋白LC3B的變化,結果顯示DeEA會明顯導致細胞內自噬體的增加。以Mitotracker偵測細胞內粒線體膜電位的變化, DeEA和MA-DeEA都會降低細胞內粒線體的功能,可能因而導致細胞的死亡。我們也以免疫螢光染色觀察藥物處理後的細胞PARP和AIF的變化,結果顯示DeEA和M-DeEA會造成AIF從粒線體移位到細胞核的現象,而且DeEA還引起PARP蛋白質表現顯著增加的情形。
綜合以上結果,我們發現DeEA、M-DeEA和MA-DeEA會對神經膠原瘤細胞U87MG產生不同的生長抑制作用。DeEA造成的細胞壞死和PARP/AIF有關,M-DeEA會造成細胞偏向細胞凋亡的死亡機制,而MA-DeEA則可能會使細胞生長週期停留在G2/M時期。
Numerous studies have demonstrated the anticancer effect of triterpenoids. A previous study from our lab has shown that Dehydroeburicoic acid (DeEA), a triterpenoid isolated from Antrodia cinnamomea (known as “niu-chang-chin” in Taiwan), can induce necrotic cell death in the human glioblastoma cell U87MG via Ca2+ overload, mitochondrial dysfunction, and calpain activation. In this thesis, we aim to further examine the mechanisms of DeEA-induced cell death in U87MG cells. In addition, we explored the anti-proliferative effects of two DeEA-derived compounds, Methyl Dehydroeburicoate (M-DeEA) and Dehydroeburicoic acid monoacetate (MA-DeEA).
Cell viability and cytotoxicity assays indicated that all three compounds can inhibit the proliferation of U87MG cells. Light microscopic analyses showed that the three compounds display differential morphological effects: DeEA induced shortening round-up and cell rupture; M-DeEA also induced cell shortenting, but with no significant rupture; and MA-DeEA induced irregular cell elongation or floating round-up. We therefore moved on to examine the differential anti-proliferation and cell death mechanisms of the three compounds.
Flow cytometric analyses with Annexin-V and propidium iodide labeling showed that DeEA significantly enhanced necrotic cell death, but that both M-DeEA and MA-DeEA moderately increased apoptotic cell death. The results of AO/EtBr staining assay also supported the idea that M-DeEA induced apoptosis. Pre-treatment with the caspase inhibitor zVAD-fmk, however, failed to significantly block MA-DeEA-induced apoptotic cell death. On the other hand, cell cycle analyses with PI labeling suggested that MA-DeEA induced cell cycle arrest at the G2/M phase.
Immunofluoresence staining of LC3B showed that DeEA significantly enhanced the presence of autophagosomes, Examination of the mitochondrial membrane potential with Mitotracker demonstrated that both DeEA and MA-DeEA disrupted the function of mitochondria, which in turn may induce cell death. Immunofluoresence staining of PARP and AIF further showed that both DeEA and MA-DeEA induced the translocation of AIF from mitochondria to nucleus, and that DeEA notably enhanced the expression of PARP.
In summary, we have identified differential cell death effects in U87MG cells by DeEA, M-DeEA, and MA-DeEA: DeEA causes PARP/AIF-related necrosis; M-DeEA triggers apoptotic cell death; and MA-DeEA probably induces cell cycle arrest at the G2/M phase.
目錄.................................................................................................................................i
圖次...............................................................................................................................iv
英文縮寫表...................................................................................................................vi
中文摘要......................................................................................................................vii
英文摘要.......................................................................................................................ix
第一章 導論
1.1 牛樟芝 (Antrodia cinnamomea)....................................................................1
1.2 去氫齒孔酸 (Dehydroeburicoic acid, DeEA)...............................................2
1.3 細胞週期 (Cell cyle).....................................................................................2
1.4 細胞死亡 (Cell death)...................................................................................4
1.4.1 細胞凋亡 (Apoptosis).........................................................................4
1.4.2 細胞自噬 (Autophagy).......................................................................6
1.4.3 細胞壞死 (Necrosis)...........................................................................8
1.5 神經膠原瘤細胞 (Glioblastoma)................................................................10
1.6 研究目的 (Aim of the study)......................................................................11
第二章 材料與方法
2.1 細胞培養 (Cell culture)..............................................................................13
2.1.1 人類神經膠原瘤細胞 (U87MG cell line)........................................13
2.1.2 人類神經膠原癌細胞株 (GBM 8401 cell line)...............................13
2.1.3 繼代培養 (Subculture)......................................................................13
2.2 藥物處理與加入 (Drugs treatment)...........................................................14
2.3 細胞存活分析 (MTT cell viability assay)..................................................14
2.4 倒立式顯微鏡照相 (Phase contrast photo)................................................15
2.5 細胞毒性檢測乳酸去氫酶 (LDH releasing assay)....................................15
2.6 流式細胞儀分析 (Annexin V and propidium iodide double stain)............16
2.7 細胞週期測定 (Propidium iodide stain).....................................................17
2.8 凋亡蛋白酵素抑制劑測試 (Caspase inhibitor test, zVAD-fmk)...............17
2.9 Acridine orange和Ethidium bromide染色 (AO/EtBr stain)......................18
2.10 細胞螢光染色 (Flourence stain).................................................................18
2.11 西方墨點法 (Western blotting)...................................................................19
2.12 數據統計分析 (Software and data analysis)...............................................20
第三章 實驗結果
3.1 利用MTT assay來檢測DeEA以及兩種衍生物是否會影響細胞生長....21
3.2 以倒立式顯微鏡觀察細胞經過DeEA及其衍生物處理後的形態變化...21
3.3 利用LDH assay觀察細胞經過三種藥物處理24小時,細胞破裂死亡的 狀況..............................................................................................................23
3.4 以流式細胞儀分析annexin V and propidium iodide雙重染色細胞,測定 三種DeEA藥物是否引發細胞的死亡途徑...............................................23
3.5 以流式細胞儀分析propidium iodide染色細胞,檢測三種藥物是否引發 細胞週期的變化..........................................................................................24
3.6 以Acridine orange和Ethidium bromide染色,檢測三種藥物對於U87MG 細胞膜完整性的影響..................................................................................25
3.7 以Phalloidin標示filamentous actin,檢測三種藥物對於細胞生長形態和 移動能力的影響..........................................................................................26
3.8 以MitoTracker標示細胞內粒線體的分布情形,檢測三種藥物對於細胞 能量利用的影響..........................................................................................27
3.9 以anti-LC3B抗體染色,檢測三種藥物的處理是否會引發細胞自噬......27
3.10 以抗體進行免疫染色,檢測三種藥物的處理是否會影響PARP-1會導致 粒線體釋放AIF並且移位到細胞核..........................................................28
3.11 以西方墨點法檢測PARP蛋白在控制組是否有被caspase切割的細胞凋 亡特徵..........................................................................................................29
3.12 利用LDH assay分析細胞凋亡蛋白酵素抑制劑是否會影響三種藥物所 引起之細胞反應..........................................................................................29
3.13 以西方墨點法檢測細胞週期素蛋白Cyclin A和Cyclin B1在不同神經膠 原瘤細胞株控制組的表現情形..................................................................29
3.14 以抗體進行免疫染色,檢測MA-DeEA的處理是否會引發神經膠原瘤細 胞進行細胞再分化......................................................................................30
第四章 討論
4.1 DeEA及其衍生物M-DeEA和MA-DeEA造成神經膠質瘤細胞不同生長 抑制效果的差異..........................................................................................31
4.2 DeEA及其衍生物M-DeEA和MA-DeEA造成不同的細胞死亡模式.....33
4.3 DeEA所產生的細胞壞死和MA-DeEA導致的細胞週期停滯機制.........35
4.4 問題與檢討..................................................................................................36
4.5 結論..............................................................................................................37
實驗圖表......................................................................................................................38
參考文獻......................................................................................................................56

Abraham, R.T. (2001). Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes &; development 15, 2177-2196.
Adhami, F., Liao, G., Morozov, Y.M., Schloemer, A., Schmithorst, V.J., Lorenz, J.N., Dunn, R.S., Vorhees, C.V., Wills-Karp, M., Degen, J.L., et al. (2006). Cerebral ischemia-hypoxia induces intravascular coagulation and autophagy. The American journal of pathology 169, 566-583.
Akihisa, T., Mizushina, Y., Ukiya, M., Oshikubo, M., Kondo, S., Kimura, Y., Suzuki, T., and Tai, T. (2004). Dehydrotrametenonic acid and dehydroeburiconic acid from Poria cocos and their inhibitory effects on eukaryotic DNA polymerase alpha and beta. Bioscience, biotechnology, and biochemistry 68, 448-450.
Akihisa, T., Nakamura, Y., Tokuda, H., Uchiyama, E., Suzuki, T., Kimura, Y., Uchikura, K., and Nishino, H. (2007). Triterpene acids from Poria cocos and their anti-tumor-promoting effects. Journal of natural products 70, 948-953.
Ame, J.C., Spenlehauer, C., and de Murcia, G. (2004). The PARP superfamily. BioEssays : news and reviews in molecular, cellular and developmental biology 26, 882-893.
Benes, P., Vetvicka, V., and Fusek, M. (2008). Cathepsin D--many functions of one aspartic protease. Critical reviews in oncology/hematology 68, 12-28.
Berger, N.A., Sims, J.L., Catino, D.M., and Berger, S.J. (1983). Poly(ADP-ribose) polymerase mediates the suicide response to massive DNA damage: studies in normal and DNA-repair defective cells. Princess Takamatsu symposia 13, 219-226.
Broker, L.E., Kruyt, F.A., and Giaccone, G. (2005). Cell death independent of caspases: a review. Clinical cancer research : an official journal of the American Association for Cancer Research 11, 3155-3162.
Bucher, N., and Britten, C.D. (2008). G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer. British journal of cancer 98, 523-528.
Cam, H., and Dynlacht, B.D. (2003). Emerging roles for E2F: beyond the G1/S transition and DNA replication. Cancer cell 3, 311-316.
Chaigne-Delalande, B., Guidicelli, G., Couzi, L., Merville, P., Mahfouf, W., Bouchet, S., Molimard, M., Pinson, B., Moreau, J.F., and Legembre, P. (2008). The immunosuppressor mycophenolic acid kills activated lymphocytes by inducing a nonclassical actin-dependent necrotic signal. Journal of immunology 181, 7630-7638.
Chang, T.T., and Chou, W.N. (1995). Antrodia cinnamomea sp. nov. on Cinnamomum kanehirai in Taiwan. Mycological Research 99, 756-758.
Chen, J., Tian, R., Qiu, M., Lu, L., Zheng, Y., and Zhang, Z. (2008). Trinorcucurbitane and cucurbitane triterpenoids from the roots of Momordica charantia. Phytochemistry 69, 1043-1048.
Chen, J.C., Lin, W.H., Chen, C.N., Sheu, S.J., Huang, S.J., and Chen, Y.L. (2001). Development of Antrodia Camphorata Mycelium with Submerge Culture. Fungal Science 16, 7-22.
Chen, Y., Azad, M.B., and Gibson, S.B. (2009). Superoxide is the major reactive oxygen species regulating autophagy. Cell death and differentiation 16, 1040-1052.
Cory, S., and Adams, J.M. (2002). The Bcl2 family: regulators of the cellular life-or-death switch. Nature reviews Cancer 2, 647-656.
Cuervo, A.M. (2006). Autophagy in neurons: it is not all about food. Trends in molecular medicine 12, 461-464.
D'Amours, D., Desnoyers, S., D'Silva, I., and Poirier, G.G. (1999). Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. The Biochemical journal 342 ( Pt 2), 249-268.
Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., Cuny, G.D., Mitchison, T.J., Moskowitz, M.A., and Yuan, J. (2005). Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nature chemical biology 1, 112-119.
Delavallee, L., Cabon, L., Galan-Malo, P., Lorenzo, H.K., and Susin, S.A. (2011). AIF-mediated caspase-independent necroptosis: a new chance for targeted therapeutics. IUBMB life 63, 221-232.
Deng, J.Y., Chen, S.J., Jow, G.M., Hsueh, C.W., and Jeng, C.J. (2009). Dehydroeburicoic acid induces calcium- and calpain-dependent necrosis in human U87MG glioblastomas. Chemical research in toxicology 22, 1817-1826.
Deretic, V. (2010). Autophagy in infection. Current opinion in cell biology 22, 252-262.
Du, L., Zhang, X., Han, Y.Y., Burke, N.A., Kochanek, P.M., Watkins, S.C., Graham, S.H., Carcillo, J.A., Szabo, C., and Clark, R.S. (2003). Intra-mitochondrial poly(ADP-ribosylation) contributes to NAD+ depletion and cell death induced by oxidative stress. The Journal of biological chemistry 278, 18426-18433.
Du, Y.C., Chang, F.R., Wu, T.Y., Hsu, Y.M., El-Shazly, M., Chen, C.F., Sung, P.J., Lin, Y.Y., Lin, Y.H., Wu, Y.C., et al. (2012). Antileukemia component, dehydroeburicoic acid from Antrodia camphorata induces DNA damage and apoptosis in vitro and in vivo models. Phytomedicine : international journal of phytotherapy and phytopharmacology 19, 788-796.
Dwivedi, M., and Ahnn, J. (2009). Autophagy--is it a preferred route for lifespan extension? BMB reports 42, 62-71.
Edinger, A.L., and Thompson, C.B. (2004). Death by design: apoptosis, necrosis and autophagy. Current opinion in cell biology 16, 663-669.
Evan, G.I., and Vousden, K.H. (2001). Proliferation, cell cycle and apoptosis in cancer. Nature 411, 342-348.
Fang, Y., Liu, T., Wang, X., Yang, Y.M., Deng, H., Kunicki, J., Traganos, F., Darzynkiewicz, Z., Lu, L., and Dai, W. (2006). BubR1 is involved in regulation of DNA damage responses. Oncogene 25, 3598-3605.
Fink, S.L., and Cookson, B.T. (2005). Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infection and immunity 73, 1907-1916.
Fouquet, S., Lugo-Martinez, V.H., Faussat, A.M., Renaud, F., Cardot, P., Chambaz, J., Pincon-Raymond, M., and Thenet, S. (2004). Early loss of E-cadherin from cell-cell contacts is involved in the onset of Anoikis in enterocytes. The Journal of biological chemistry 279, 43061-43069.
Freije, W.A., Castro-Vargas, F.E., Fang, Z., Horvath, S., Cloughesy, T., Liau, L.M., Mischel, P.S., and Nelson, S.F. (2004). Gene expression profiling of gliomas strongly predicts survival. Cancer research 64, 6503-6510.
Fryer, H.J., Knox, R.J., Strittmatter, S.M., and Kalb, R.G. (1999). Excitotoxic death of a subset of embryonic rat motor neurons in vitro. Journal of neurochemistry 72, 500-513.
Fung, C., Lock, R., Gao, S., Salas, E., and Debnath, J. (2008). Induction of autophagy during extracellular matrix detachment promotes cell survival. Molecular biology of the cell 19, 797-806.
Galaz, S., Espada, J., Stockert, J.C., Pacheco, M., Sanz-Rodriguez, F., Arranz, R., Rello, S., Canete, M., Villanueva, A., Esteller, M., et al. (2005). Loss of E-cadherin mediated cell-cell adhesion as an early trigger of apoptosis induced by photodynamic treatment. Journal of cellular physiology 205, 86-96.
Galluzzi, L., and Kroemer, G. (2008). Necroptosis: a specialized pathway of programmed necrosis. Cell 135, 1161-1163.
Golstein, P., and Kroemer, G. (2007). Cell death by necrosis: towards a molecular definition. Trends in biochemical sciences 32, 37-43.
Guidicelli, G., Chaigne-Delalande, B., Dilhuydy, M.S., Pinson, B., Mahfouf, W., Pasquet, J.M., Mahon, F.X., Pourquier, P., Moreau, J.F., and Legembre, P. (2009). The necrotic signal induced by mycophenolic acid overcomes apoptosis-resistance in tumor cells. PloS one 4, e5493.
Ha, H.C., and Snyder, S.H. (1999). Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proceedings of the National Academy of Sciences of the United States of America 96, 13978-13982.
Hall, A. (1998). Rho GTPases and the actin cytoskeleton. Science 279, 509-514.
Haupt, Y., Maya, R., Kazaz, A., and Oren, M. (1997). Mdm2 promotes the rapid degradation of p53. Nature 387, 296-299.
Hengartner, M.O. (2000). The biochemistry of apoptosis. Nature 407, 770-776.
Hermeking, H. (2003). The 14-3-3 cancer connection. Nature reviews Cancer 3, 931-943.
Hsiao, G., Shen, M.Y., Lin, K.H., Lan, M.H., Wu, L.Y., Chou, D.S., Lin, C.H., Su, C.H., and Sheu, J.R. (2003). Antioxidative and hepatoprotective effects of Antrodia camphorata extract. Journal of agricultural and food chemistry 51, 3302-3308.
Ivanov, V.N., Bhoumik, A., and Ronai, Z. (2003). Death receptors and melanoma resistance to apoptosis. Oncogene 22, 3152-3161.
Jaeger, P.A., and Wyss-Coray, T. (2009). All-you-can-eat: autophagy in neurodegeneration and neuroprotection. Molecular neurodegeneration 4, 16.
Kanai, M., Hanashiro, K., Kim, S.H., Hanai, S., Boulares, A.H., Miwa, M., and Fukasawa, K. (2007). Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation. Nature cell biology 9, 1175-1183.
Kaufmann, S.H., and Earnshaw, W.C. (2000). Induction of apoptosis by cancer chemotherapy. Experimental cell research 256, 42-49.
Kerr, J.F., Wyllie, A.H., and Currie, A.R. (1972). Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British journal of cancer 26, 239-257.
Kim, M.Y., Zhang, T., and Kraus, W.L. (2005). Poly(ADP-ribosyl)ation by PARP-1: 'PAR-laying' NAD+ into a nuclear signal. Genes &; development 19, 1951-1967.
Klionsky, D.J., Abeliovich, H., Agostinis, P., Agrawal, D.K., Aliev, G., Askew, D.S., Baba, M., Baehrecke, E.H., Bahr, B.A., Ballabio, A., et al. (2008). Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 4, 151-175.
Klionsky, D.J., and Emr, S.D. (2000). Autophagy as a regulated pathway of cellular degradation. Science 290, 1717-1721.
Kubbutat, M.H., Jones, S.N., and Vousden, K.H. (1997). Regulation of p53 stability by Mdm2. Nature 387, 299-303.
Lawson, H.C., Sampath, P., Bohan, E., Park, M.C., Hussain, N., Olivi, A., Weingart, J., Kleinberg, L., and Brem, H. (2007). Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience. Journal of neuro-oncology 83, 61-70.
Lee, J.A. (2009). Autophagy in neurodegeneration: two sides of the same coin. BMB reports 42, 324-330.
Legler, J.M., Ries, L.A., Smith, M.A., Warren, J.L., Heineman, E.F., Kaplan, R.S., and Linet, M.S. (1999). Cancer surveillance series [corrected]: brain and other central nervous system cancers: recent trends in incidence and mortality. Journal of the National Cancer Institute 91, 1382-1390.
Leve, F., de Souza, W., and Morgado-Diaz, J.A. (2008). A cross-link between protein kinase A and Rho-family GTPases signaling mediates cell-cell adhesion and actin cytoskeleton organization in epithelial cancer cells. The Journal of pharmacology and experimental therapeutics 327, 777-788.
Li, D.D., Guo, J.F., Huang, J.J., Wang, L.L., Deng, R., Liu, J.N., Feng, G.K., Xiao, D.J., Deng, S.Z., Zhang, X.S., et al. (2010). Rhabdastrellic acid-A induced autophagy-associated cell death through blocking Akt pathway in human cancer cells. PloS one 5, e12176.
Liu, C., Gao, Y., Barrett, J., and Hu, B. (2010). Autophagy and protein aggregation after brain ischemia. Journal of neurochemistry 115, 68-78.
Liu, D.Z., Liang, H.J., Chen, C.H., Su, C.H., Lee, T.H., Huang, C.T., Hou, W.C., Lin, S.Y., Zhong, W.B., Lin, P.J., et al. (2007). Comparative anti-inflammatory characterization of wild fruiting body, liquid-state fermentation, and solid-state culture of Taiwanofungus camphoratus in microglia and the mechanism of its action. Journal of ethnopharmacology 113, 45-53.
Liu, X., Harriman, J.F., and Schnellmann, R.G. (2002). Cytoprotective properties of novel nonpeptide calpain inhibitors in renal cells. The Journal of pharmacology and experimental therapeutics 302, 88-94.
Liu, X., Rainey, J.J., Harriman, J.F., and Schnellmann, R.G. (2001). Calpains mediate acute renal cell death: role of autolysis and translocation. American journal of physiology Renal physiology 281, F728-738.
Lock, R., and Debnath, J. (2008). Extracellular matrix regulation of autophagy. Current opinion in cell biology 20, 583-588.
Lockshin, R.A., and Zakeri, Z. (2001). Programmed cell death and apoptosis: origins of the theory. Nature reviews 2, 545-550.
Lu, W., Pochampally, R., Chen, L., Traidej, M., Wang, Y., and Chen, J. (2000). Nuclear exclusion of p53 in a subset of tumors requires MDM2 function. Oncogene 19, 232-240.
Lum, J.J., DeBerardinis, R.J., and Thompson, C.B. (2005). Autophagy in metazoans: cell survival in the land of plenty. Nature reviews 6, 439-448.
Maiuri, M.C., Zalckvar, E., Kimchi, A., and Kroemer, G. (2007). Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nature reviews 8, 741-752.
Majno, G., and Joris, I. (1995). Apoptosis, oncosis, and necrosis. An overview of cell death. The American journal of pathology 146, 3-15.
Malumbres, M., and Barbacid, M. (2009). Cell cycle, CDKs and cancer: a changing paradigm. Nature reviews Cancer 9, 153-166.
Marnett, L.J. (2000). Oxyradicals and DNA damage. Carcinogenesis 21, 361-370.
Martinez-Vicente, M., and Cuervo, A.M. (2007). Autophagy and neurodegeneration: when the cleaning crew goes on strike. Lancet neurology 6, 352-361.
Mizushima, N., Levine, B., Cuervo, A.M., and Klionsky, D.J. (2008). Autophagy fights disease through cellular self-digestion. Nature 451, 1069-1075.
Mizushima, N., and Yoshimori, T. (2007). How to interpret LC3 immunoblotting. Autophagy 3, 542-545.
Mizushina, Y., Akihisa, T., Ukiya, M., Murakami, C., Kuriyama, I., Xu, X., Yoshida, H., and Sakaguchi, K. (2004). A novel DNA topoisomerase inhibitor: dehydroebriconic acid, one of the lanostane-type triterpene acids from Poria cocos. Cancer science 95, 354-360.
Monaco, L., Kolthur-Seetharam, U., Loury, R., Murcia, J.M., de Murcia, G., and Sassone-Corsi, P. (2005). Inhibition of Aurora-B kinase activity by poly(ADP-ribosyl)ation in response to DNA damage. Proceedings of the National Academy of Sciences of the United States of America 102, 14244-14248.
Monastyrska, I., Rieter, E., Klionsky, D.J., and Reggiori, F. (2009). Multiple roles of the cytoskeleton in autophagy. Biological reviews of the Cambridge Philosophical Society 84, 431-448.
Moon, D.O., Kim, M.O., Kang, S.H., Lee, K.J., Heo, M.S., Choi, K.S., Choi, Y.H., and Kim, G.Y. (2008). Induction of G2/M arrest, endoreduplication, and apoptosis by actin depolymerization agent pextenotoxin-2 in human leukemia cells, involving activation of ERK and JNK. Biochemical pharmacology 76, 312-321.
Murakami, H., and Nurse, P. (2000). DNA replication and damage checkpoints and meiotic cell cycle controls in the fission and budding yeasts. The Biochemical journal 349, 1-12.
Nicotera, P., Leist, M., and Manzo, L. (1999). Neuronal cell death: a demise with different shapes. Trends in pharmacological sciences 20, 46-51.
Nishimura, Y., and Lemasters, J.J. (2001). Glycine blocks opening of a death channel in cultured hepatic sinusoidal endothelial cells during chemical hypoxia. Cell death and differentiation 8, 850-858.
Ohgoh, M., Shimizu, H., Ogura, H., and Nishizawa, Y. (2000). Astroglial trophic support and neuronal cell death: influence of cellular energy level on type of cell death induced by mitochondrial toxin in cultured rat cortical neurons. Journal of neurochemistry 75, 925-933.
Poirier, M.C. (2004). Chemical-induced DNA damage and human cancer risk. Nature reviews Cancer 4, 630-637.
Price, D.L., Sisodia, S.S., and Borchelt, D.R. (1998). Genetic neurodegenerative diseases: the human illness and transgenic models. Science 282, 1079-1083.
Rao, Y.K., Fang, S.H., and Tzeng, Y.M. (2007). Evaluation of the anti-inflammatory and anti-proliferation tumoral cells activities of Antrodia camphorata, Cordyceps sinensis, and Cinnamomum osmophloeum bark extracts. Journal of ethnopharmacology 114, 78-85.
Saxena, A., Wong, L.H., Kalitsis, P., Earle, E., Shaffer, L.G., and Choo, K.H. (2002). Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc. Human molecular genetics 11, 2319-2329.
Schwarz, M., Andrade-Navarro, M.A., and Gross, A. (2007). Mitochondrial carriers and pores: key regulators of the mitochondrial apoptotic program? Apoptosis : an international journal on programmed cell death 12, 869-876.
Senderowicz, A.M., and Sausville, E.A. (2000). Preclinical and clinical development of cyclin-dependent kinase modulators. Journal of the National Cancer Institute 92, 376-387.
Sheikh, A.M., Li, X., Wen, G., Tauqeer, Z., Brown, W.T., and Malik, M. (2010). Cathepsin D and apoptosis related proteins are elevated in the brain of autistic subjects. Neuroscience 165, 363-370.
Shen, C.C., Kuo, Y.C., Huang, R.L., Lin, L.C., Don, M.J., Chang, T.T., and Chou, C.J. (2003). New ergostane and lanostane from Antrodia camphorata. J Chin Med 14, 247-258.
Stewart, Z.A., Westfall, M.D., and Pietenpol, J.A. (2003). Cell-cycle dysregulation and anticancer therapy. Trends in pharmacological sciences 24, 139-145.
Stupp, R., Hegi, M.E., Gilbert, M.R., and Chakravarti, A. (2007). Chemoradiotherapy in malignant glioma: standard of care and future directions. J Clin Oncol 25, 4127-4136.
Surawicz, T.S., Davis, F., Freels, S., Laws, E.R., Jr., and Menck, H.R. (1998). Brain tumor survival: results from the National Cancer Data Base. Journal of neuro-oncology 40, 151-160.
Sweet, S., and Singh, G. (1995). Accumulation of human promyelocytic leukemic (HL-60) cells at two energetic cell cycle checkpoints. Cancer research 55, 5164-5167.
Taylor, W.R., and Stark, G.R. (2001). Regulation of the G2/M transition by p53. Oncogene 20, 1803-1815.
Timmer, T., de Vries, E.G., and de Jong, S. (2002). Fas receptor-mediated apoptosis: a clinical application? The Journal of pathology 196, 125-134.
Tsai, Z.T., and Liaw, S.L. (1985). The use and the effect of Ganoderma. Sheng-Yun Publisher Inc Taichung, Taiwan, 116-117.
Tuloup-Minguez, V., Greffard, A., Codogno, P., and Botti, J. (2011). Regulation of autophagy by extracellular matrix glycoproteins in HeLa cells. Autophagy 7, 27-39.
Ullman, E., Fan, Y., Stawowczyk, M., Chen, H.M., Yue, Z., and Zong, W.X. (2008). Autophagy promotes necrosis in apoptosis-deficient cells in response to ER stress. Cell death and differentiation 15, 422-425.
Walker, N.I., Harmon, B.V., Gobe, G.C., and Kerr, J.F. (1988). Patterns of cell death. Methods and achievements in experimental pathology 13, 18-54.
Wang, H., Haridas, V., Gutterman, J.U., and Xu, Z.X. (2010). Natural triterpenoid avicins selectively induce tumor cell death. Communicative &; integrative biology 3, 205-208.
Waring, P. (2005). Redox active calcium ion channels and cell death. Archives of biochemistry and biophysics 434, 33-42.
Wen, Y.D., Sheng, R., Zhang, L.S., Han, R., Zhang, X., Zhang, X.D., Han, F., Fukunaga, K., and Qin, Z.H. (2008). Neuronal injury in rat model of permanent focal cerebral ischemia is associated with activation of autophagic and lysosomal pathways. Autophagy 4, 762-769.
Wiencke, J.K. (2004). Impact of race/ethnicity on molecular pathways in human cancer. Nature reviews Cancer 4, 79-84.
Woodgate, A., MacGibbon, G., Walton, M., and Dragunow, M. (1999). The toxicity of 6-hydroxydopamine on PC12 and P19 cells. Brain research 69, 84-92.
Wu, S.-H., Ryvarden, L., and Chang, T.-T. (1997). Antrodia camphorata ("niu-chang-chih"), new combination of a medicinal fungus in Taiwan. Bot Bull Acad Sin 38, 273-275.
Xiong, Z.G., Zhu, X.M., Chu, X.P., Minami, M., Hey, J., Wei, W.L., MacDonald, J.F., Wemmie, J.A., Price, M.P., Welsh, M.J., et al. (2004). Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell 118, 687-698.
Xu, Z.X., Liang, J., Haridas, V., Gaikwad, A., Connolly, F.P., Mills, G.B., and Gutterman, J.U. (2007). A plant triterpenoid, avicin D, induces autophagy by activation of AMP-activated protein kinase. Cell death and differentiation 14, 1948-1957.
Yang, S.W., Shen, Y.C., and Chen, C.H. (1996). Steroids and triterpenoids of Antodia cinnamomea—A fungus parasitic on Cinnamomum micranthum. Phytochemistry 41, 1389-1392.
Yang, Z., and Klionsky, D.J. (2009). An overview of the molecular mechanism of autophagy. Current topics in microbiology and immunology 335, 1-32.
Yao, K.C., Komata, T., Kondo, Y., Kanzawa, T., Kondo, S., and Germano, I.M. (2003). Molecular response of human glioblastoma multiforme cells to ionizing radiation: cell cycle arrest, modulation of the expression of cyclin-dependent kinase inhibitors, and autophagy. Journal of neurosurgery 98, 378-384.
Yin, D., Wakimoto, N., Xing, H., Lu, D., Huynh, T., Wang, X., Black, K.L., and Koeffler, H.P. (2008). Cucurbitacin B markedly inhibits growth and rapidly affects the cytoskeleton in glioblastoma multiforme. International journal of cancer Journal international du cancer 123, 1364-1375.
Ying, W., Garnier, P., and Swanson, R.A. (2003). NAD+ repletion prevents PARP-1-induced glycolytic blockade and cell death in cultured mouse astrocytes. Biochemical and biophysical research communications 308, 809-813.
Zhang, J., Huang, Y., Kikuchi, T., Tokuda, H., Suzuki, N., Inafuku, K., Miura, M., Motohashi, S., Suzuki, T., and Akihisa, T. (2012). Cucurbitane triterpenoids from the leaves of Momordica charantia, and their cancer chemopreventive effects and cytotoxicities. Chemistry &; biodiversity 9, 428-440.
Zhang, T., Liu, X., Li, Q., Wang, J., Jia, W., and Sun, X. (2010). Exacerbation of ischemia-induced amyloid-beta generation by diabetes is associated with autophagy activation in mice brain. Neuroscience letters 479, 215-220.
Zong, W.X., and Thompson, C.B. (2006). Necrotic death as a cell fate. Genes &; development 20, 1-15.

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