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研究生:魏羽橙
研究生(外文):Yu-Cheng Wei
論文名稱:蛹蟲草發酵產物萃取液誘導人類及犬乳癌細胞凋亡機制之探討
論文名稱(外文):Studies on the mechanism of inducing human and canine breast cancer cells apoptosis by fermentative extract from Cordyceps militaris
指導教授:陳淑德鄭永祥鄭永祥引用關係
指導教授(外文):Su-Der ChenYeong-Hsiang Cheng
學位類別:碩士
校院名稱:國立宜蘭大學
系所名稱:生物技術研究所碩士班
學門:農業科學學門
學類:畜牧學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:中文
論文頁數:109
中文關鍵詞:蛹蟲草腺苷蟲草素細胞凋亡
外文關鍵詞:Cordyceps militarisadenosinecordycepinapoptosis
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蛹蟲草(Cordyceps militaris)已知為罕見之中國傳統藥用蕈類。在傳統的中藥裡蟲草已經使用來治療許多疾病,包括呼吸道及肺部疾病、腎臟、肝臟、心血管、性慾減退及高血脂疾病等。它也可以調節免疫功能及作為癌症治療。蛹蟲草固態發酵代謝產物包括腺苷及蟲草素具有抗腫瘤的活性。本研究之目的,先利用蛹蟲草固態發酵,生產其代謝產物蟲草素及腺苷,再探討其萃取液對乳癌細胞凋亡之影響。本研究以小麥為基質,水分含量控制在50%,再加入5%各種不同氮源包括酵母抽物、酵母粉及蛋白腖在22℃下進行蛹蟲草固態發酵,並利用HPLC進行蟲草素及腺苷之定量分析,結果指出以酵母粉作為氮源時,於固態發酵第二十一天的蟲草素產量為5088μg/g,明顯高於以蛋白腖及酵母出抽物作為氮源者,而其腺苷在第十七天可達最高產量為258μg/g。將熱水萃取後之蛹蟲草發酵產物,分別對犬乳癌細胞株(DTK-SM2和DTK-SME-like)及人類乳癌細胞株(HCC 1937)進行細胞培養,結果顯示當熱水萃取液含10μg/mL蟲草素時,培養12~24小時後於顯微鏡下觀察發現,可誘導犬及人類乳癌細胞株產生凋亡小體,萃取其DNA並以電泳分析發現DNA 片段化的現象,以西方點墨分析法發現Pro-caspase及PARP蛋白質表現量下降,故蛹蟲草固態發酵產物之熱水萃取液,具有抗腫瘤之活性,而誘導乳癌細胞株凋亡可能與caspase 3之路徑有關。
Cordyceps militaris, is a rare and exotic Chinese medicinal mushroom. The traditional Chinese medicine, C. militaris has been used to cure many diseases, including respiration, pulmonary, renal, liver and cardiovascular diseases, hyposexuality, and hyperlipidemia. It is also used to regulate immune function and as an adjunct in cancer therapy. The metabolites such as adenosine and cordycepin in fermentation product of Cordyceps militaris showed an anti-tumor activity. The objectives of this study were to produce cordycepin and adenosine from Cordyceps militaris solid fermentation and to investigate the effect cordycepin on the apoptosis of breast cancer cells. Wheat with 50% moisture content was the solid culture containing 5% different nitrogen sources such as, yeast extract, yeast powder and peptone, for C. militaris solid fermentation. The production of cordycepin and adenosine was monitored by HPLC during fermentation. The highest cordycepin and adenosine production appeared 5088.4μg/g on the 21th day and 258.7μg/g on the 17th day C. militaris fermentation by feeding yeast powder, respectively. The hot-water extracts from Cordyceps militaris were co-cultured with canine mammary cell lines, DTK-SM2 and DTK-SME-like, human mammary cell lines HCC 1937. The results revealed that 10μg/mL cordycepin added in a co-culture for 12~24 hrs could induced the production of apoptotic body in canine and human mammary cell lines under microscopic observation. DNA fragmentation was also demonstrated by electrophoresis. Decreasing CAD, Pro-caspase 3 and PARP protein expression was observed by Western blot analysis. Therefore, Cordyceps militaris hot water extract could induce apoptosis in human and canine mammary carcinoma cell lines, and apoptosis pathway may be related to caspase 3 pathway.
總目錄
中文摘要………………………………………………………………………I
英文摘要………………………………………………………………………II
誌謝…………………………………………………………………………III
總目錄…………………………………………………………………………V
表目錄…………………………………………………………………………IX
圖目錄…………………………………………………………………………X
壹、文獻回顧…………………………………………………………………1
1、前言…………………………………………………………………………1
2、蛹蟲草的特徵介紹…………………………………………………………2
3、蛹蟲草的化學成份……………………………………………………2
4、發酵方法………………………………………………………………3
5、影響蟲草深層發酵菌絲的生長及蟲草素生成因素…………………5
5.1、起始pH值及溫度……………………………………………………5
5.2、碳源……………………………………………………………………6
5.3、氮源……………………………………………………………………7
6、中醫書上的功效…………………………………………………………8
6.1、抗氧化性………………………………………………………………8
6.2、降血糖…………………………………………………………………10
6.3、抗腫瘤與抗癌作用……………………………………………………11
6.4、免疫調節………………………………………………………………13
6.5、性功能調節……………………………………………………………14
7、細胞凋亡…………………………………………………………………15
7.1、細胞凋亡簡介…………………………………………………………15
7.2、細胞凋亡的調節………………………………………………………15
7.3、Bcl-2 蛋白家族………………………………………………………17
7.4、接收器調控的細胞凋亡途徑(receptor- mediated apoptosis) …………17
7.5、Caspases…………………………………………………………………20
7.6、細胞凋亡內在途徑………………………………………………………21
7.7、熱休克蛋白調節細胞凋亡………………………………………………23
7.8、二磷酸腺苷核糖多聚酶(Poly (ADP-ribose) polymerase, PARP) ………24
貳、材料與方法………………………………………………………………26
1、固態發酵試藥………………………………………………………………26
2、固態發酵儀器………………………………………………………………26
3、細胞培養試藥………………………………………………………………27
4、實驗儀器……………………………………………………………………28
5、蛹蟲草(Cordyceps militaris)固態發酵……………………………………29
6、固態培養基……………………………………………………………29
7、腺苷(adenosine)及蟲草素(cordycepin)的分析……………………………30
8、蛹蟲草熱水萃取物(CMHW)之製備………………………………………31
9、細胞培養……………………………………………………………………31
10、細胞存活率(viability)測定………………………………………………32
11、細胞形態變化觀察………………………………………………………33
12、Hoechst 33258 螢光染色…………………………………………………34
13、西方點墨法分析(Western blot analysis) …………………………………34
13.1、蛋白質定量法(Bradford dye-binding method) ………………………34
13.2、SDS-PAGE電泳………………………………………………………36
14、Caspase活性分析………………………………………………………37
15、DNA片斷化(DNA fragmentation)分析…………………………………38
16、Annexin V…………………………………………………………………39
17、TUNEL (TdT-mediated dUTP nick end labeling) ………………………39
參、結果與討論………………………………………………………………41
1、蛹蟲草固態發酵產物萃取物腺苷及蟲草素分析…………………………41
2、細胞毒性測試………………………………………………………………42
3、細胞形態變化觀察…………………………………………………………44
4、Hoechst 33258染色分析…………………………………………………46
5、西方點墨分析法(Western blot) ……………………………………………46
6、Caspase activity……………………………………………………………48
7、DNA片段化分析…………………………………………………………50
8、Annexin V分析……………………………………………………………51
9、TUNEL分析………………………………………………………………51
肆、結論………………………………………………………………………53
伍、參考文獻…………………………………………………………………86


























表目錄
表 1.1、細胞凋亡機制演化保留………………………………………………16



































圖目錄
圖 1.1、蛹蟲草中adenosine、cordycepin及ergosterol化學結構式…………3
圖 1.2、蟲草固態發酵…………………………………………………………4
圖 1.3、蟲草液態發酵…………………………………………………………4
圖 1.4、生物工程流程圖………………………………………………………5
圖 1.5、接受器調控的細胞凋亡途徑…………………………………………19
圖 1.6、細胞凋亡內源路徑……………………………………………………22
圖 1.7、HSP 60與Bax交互作用及細胞凋亡誘導壓力的影響………………24
圖 3.1、以蟲草素標準品溶液作為標準曲線…………………………………54
圖 3.2、以腺苷標準品溶液作為標準曲線……………………………………55
圖3.3、以不同氮源作為蛹蟲草固態發酵培養基進行發酵21天之腺苷濃度變化……………………………………………………………………56
圖3.4、以不同氮源作為蛹蟲草固態發酵培養基進行發酵21天之蟲草素濃度變化…………………………………………………………………57
圖 3.5、以不同濃度酵母粉作為蛹蟲草固態發酵培養基進行發酵7、14、21天之蟲草素濃度變化…………………………………………………58
圖 3.6、以MTT呈色法評估蛹蟲草固態發酵萃取液對人類乳癌細胞株(HCC 1937)存活率的影響…………………………………………………59
圖 3.7、以MTT呈色法評估蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK SM2) 存活率的影響……………………………………………………60
圖 3.8、以MTT呈色法評估蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK-SME like)存活率的影響…………………………………………61
圖 3.9、人類乳癌細胞株HCC 1937添加蛹蟲草熱水萃取物後形態上之變化………………………………………………………………………62
圖 3.10、犬乳癌細胞株DTK SM2添加蛹蟲草熱水萃取物後形態上之變化………………………………………………………………………64
圖 3.11、犬乳癌細胞株DTK SME-like添加蛹蟲草熱水萃取物後形態上之變化……………………………………………………………………66
圖 3.12、以Hoechest 33258呈色觀察蛹蟲草固態發酵萃取液對人類乳癌細胞株(HCC 1937)細胞凋亡的影響…………………………………68
圖 3.13、以Hoechest 33258呈色觀察蛹蟲草固態發酵萃取液對犬乳癌細胞
株(DTK SM2)細胞凋亡的影響……………………………………69
圖 3.14、以Hoechest 33258呈色觀察蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK SME like )細胞凋亡的影響………………………………70
圖 3.15、蛹蟲草固態發酵萃取液對人類乳癌細胞株(HCC 1937) caspase-3、CAD及PARP表現量影響………………………………………………71
圖 3.16、蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK SM2) caspase-3、CAD及PARP的影響…………………………………………………72
圖 3.17、蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK-SME like) caspase-3、CAD及PARP的影響………………………………………73
圖 3.18、以caspase活性分析蛹蟲草固態發酵萃取液對人類乳癌細胞株(HCC 1937)細胞凋亡的影響…………………………………………74
圖 3.19、以caspase活性分析蛹蟲草固態發酵萃取液對犬乳癌細胞株 (DTK-SM2)細胞凋亡的影響………………………………………75
圖 3.20、以caspase活性分析蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK-SME like)細胞凋亡的影響…………………………………76
圖 3.21、以DNA片斷化分析蛹蟲草固態發酵萃取液對人類乳癌細胞株(HCC 1937)細胞凋亡的影響………………………………………77
圖 3.22、以DNA片斷化分析蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK-SM2)細胞凋亡的影響………………………………………78
圖 3.23、以DNA片斷化分析蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK-SME like)細胞凋亡的影響……………………………………79
圖 3.24、以Annexin V螢光呈色觀察蛹蟲草固態發酵萃取液對人類乳癌細胞株(HCC 1937)細胞凋亡的影響…………………………………80
圖 3.25、以Annexin V螢光呈色觀察蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK-SM2)細胞凋亡的影響………………………………………81
圖 3.26、以Annexin V螢光呈色觀察蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK-SME like)細胞凋亡的影響…………………………………82
圖 3.27、以TUNEL螢光呈色觀察蛹蟲草固態發酵萃取液對人類乳癌細胞株(HCC 1937)細胞凋亡的影響……………………………………83
圖 3.28、以TUNEL螢光呈色觀察蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK SM2)細胞凋亡的影響………………………………………84
圖 3.29、以TUNEL螢光呈色觀察蛹蟲草固態發酵萃取液對犬乳癌細胞株(DTK SME like)細胞凋亡的影響…………………………………85
李建良。液態培養生產冬蟲夏草菌絲體與冬蟲夏草多醣之研究。國立交通大學生物科技研究所碩士論文(2000)。
Ames, B. N. Endogenous oxidative DNA damage, aging, and cancer. Free. Radic. Res. Commun. 7, 121-128 (1989).

Ashkenazi, A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat. Rev. Cancer 2, 420-430 (2002).

Balon, T. W., Jasman, A. P. and Zhu, J. S. A fermentation product of Cordyceps sinensis increases whole-body insulin sensitivity in rats. J. Altern. Complement Med. 8, 315-323 (2002).

Beere, H. M., Wolf, B. B., Cain, K., Mosser, D. D., Mahboubi, A., Kuwana, T., Tailor, P., Morimoto, R. I., Cohen, G. M. and Green, D. R.Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nat. Cell Biol. 2, 469-475 (2000).

Behrens, T. W. and Mueller, D. L. Bcl-x and the regulation of survival in the immune system. Immunol. Res. 16, 149-160 (1997).

Bienhoff, S. E., Allen, G. K. and Berg, J. N. Release of tumor necrosis factor-alpha from bovine alveolar macrophages stimulated with bovine respiratory viruses and bacterial endotoxins. Vet. Immunol. Immunopathol. 30, 341-357 (1992).

Bohr, V., Anson, R. M., Mazur, S. and Dianov, G. Oxidative DNA damage processing and changes with aging. Toxicol. Lett. 102-103, 47-52 (1998).

Chang, C. Y., Lue, M. Y. and Pan, T. M. Determination of adenosine, cordycepin and ergosterol contents in cultivated antrodia camphorata by HPLC method. J. Food Drug Ana. 13, 338-342 (2005).

Chen, Y. C., Huang, Y. L. and Huang, B. M. Cordyceps sinensis mycelium activates PKA and PKC signal pathways to stimulate steroidogenesis in MA-10 mouse Leydig tumor cells. Int. J. Biochem. Cell Biol. 37, 214-23 (2005).

Choi, S. B., Park, C. H., Choi, M. K., Jun, D. W. and Park, S. Improvement of insulin resistance and insulin secretion by water extracts of Cordyceps militaris, Phellinus linteus, and Paecilomyces tenuipes in 90% pancreatectomized rats. Biosci. Biotechnol. Biochem. 68, 2257-2264 (2004).

Chuang, H. L., Lee, X. L.and Huang, T. C. Extracts of Tsarm Yung Chung Tsao which exhibit remarkably antioxidative and free-radical scavenging activities. J. Taiwan Normal University:Mathematics, Science and Tech. 48(1,2), 13-24 (2003)

Coleman, M. L., Sahai, E. A., Yeo, M., Bosch, M., Dewar, A. and Olson, M. F.Membrane blebbing during apoptosis results from caspase-mediated activation of ROCK I. Nat. Cell Biol. 3, 339-345 (2001).

Cory, S. and Adams, J.M. The Bcl2 family: regulators of the cellular life-or-death switch. Nat. Rev. Cancer 2, 647-656 (2002).

Danial, N.N. and Korsmeyer, S.J. Cell death: critical control points. Cell 116, 205-219 (2004).

De Laurenzi, V. and Melino, G. Apoptosis. The little devil of death. Nature 406, 135-136 (2000).

Denizot, F. and Lang, R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J. Immunol. Methods 89, 271-277 (1986).

Desnoyers, S. and Hengartner, M. O. Genetics of apoptosis. Adv. Pharmacol. 41, 35-56 (1997).

Dong, C. H. and Yao, Y. J. Nutritional requirements of mycelial growth of Cordyceps sinensis in submerged culture. J. Appl. Microbiol. 99, 483-492 (2005).

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).

Earnshaw, W. C., Martins, L. M. and Kaufmann, S. H. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu. Rev. Biochem. 68, 383-424 (1999).

Farnsworth, N.R. Ethnopharmacology and drug development. Ciba. Found. Symp. 185, 42-51; discussion 51-59 (1994).

Garcia-Calvo, M., Peterson, E. P., Leiting, B., Ruel, R., Nicholson, D. W. and Thornberry, N. A. Inhibition of human caspases by peptide-based and macromolecular inhibitors. J. Biol. Chem. 273, 32608-32613 (1998).

Garrido, C., Bruey, J. M., Fromentin, A., Hammann, A., Arrigo, A. P. and Solary, E. HSP27 inhibits cytochrome c-dependent activation of procaspase-9. Faseb. J. 13, 2061-2070 (1999).

Grutter, M. G. Caspases: key players in programmed cell death. Curr. Opin. Struct. Biol. 10, 649-655 (2000).

Gunther, S., Patterson, R.E., Kristal, A.R., Stratton, K.L. and White, E. Demographic and health-related correlates of herbal and specialty supplement use. J. Am. Diet. Assoc. 104, 27-34 (2004).

Gupta, S. and Knowlton, A.A. Cytosolic heat shock protein 60, hypoxia, and apoptosis. Circulation 106, 2727-2733 (2002).

Gupta, S. and Knowlton, A.A. HSP60, Bax, apoptosis and the heart. J. Cell Mol. Med. 9, 51-58 (2005).

Halliwell, B. Oxidative stress and neurodegeneration: where are we now? J. Neurochem. 97, 1634-1658 (2006).

Halliwell, B., Gutteridge, J. M. and Cross, C. E. Free radicals, antioxidants, and human disease: where are we now? J. Lab. Clin. Med. 119, 598-620 (1992).

Hsu, C. C., Huang, Y. L., Tsai, S. J., Sheu, C. C. and Huang, B. M. In vivo and in vitro stimulatory effects of Cordyceps sinensis on testosterone production in mouse Leydig cells. Life Sci. 73, 2127-2136 (2003).

Hsu, C. C., Tsai, S. J., Huang, Y. L. and Huang, B. M. Regulatory mechanism of Cordyceps sinensis mycelium on mouse Leydig cell steroidogenesis. FEBS. Lett. 543, 140-3 (2003).

Huang, B. M., Hsu, C. C., Tsai, S. J., Sheu, C. C. and Leu, S. F. Effects of Cordyceps sinensis on testosterone production in normal mouse Leydig cells. Life. Sci. 69, 2593-2602 (2001).

Ishii, N., Ishii, T. and Hartman, P. S. The role of the electron transport SDHC gene on lifespan and cancer. Mitochondrion 7, 24-8 (2007).

Jacobson, M. D. Apoptosis: Bcl-2-related proteins get connected. Curr. Biol. 7, R277-281 (1997).

Johnson, K. L., Vaillant, F. and Lawen, A. Protein tyrosine kinase inhibitors prevent didemnin B-induced apoptosis in HL-60 cells. FEBS. Lett. 383, 1-5 (1996).

Kaufmann, S. H., Desnoyers, S., Ottaviano, Y., Davidson, N. E. and Poirier, G. G. Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Res. 53, 3976-3985 (1993).

Kerr, J. F., Winterford, C. M. and Harmon, B. V. Apoptosis. Its significance in cancer and cancer therapy. Cancer 73, 2013-2026 (1994).

Kerr, J. F., Wyllie, A. H. and Currie, A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26, 239-257 (1972).

Kiho, T., Yamane, A., Hui, J., Usui, S. and Ukai, S. Polysaccharides in fungi. XXXVI. Hypoglycemic activity of a polysaccharide (CS-F30) from the cultural mycelium of Cordyceps sinensis and its effect on glucose metabolism in mouse liver. Biol. Pharm. Bull. 19, 294-296 (1996).

Kim, H. G., Shrestha, B.,Lim, S. Y., Yoon, D. H., Chang, W. C., Shin, D. J., Han, S. K., Park, S. M., Park, J. H., Park, H. I., Sung, J. M., Jang, Y., Chung, N., Hwang, K. C. and Kim, T. W.Cordycepin inhibits lipopolysaccharide-induced inflammation by the suppression of NF-kappaB through Akt and p38 inhibition in RAW 264.7 macrophage cells. Eur. J. Pharmacol. 545, 192-1999 (2006).

Kim, J. and Park, E.J. Cytotoxic anticancer candidates from natural resources. Curr. Med. Chem. Anticancer Agents 2, 485-537 (2002).

Kim, S. W. et al. Optimization of submerged culture process for the production of mycelial biomass and exo-polysaccharides by Cordyceps militaris C738. J. Appl. Microbiol. 94, 120-6 (2003).

Koh, J. H., Yu, K. W., Suh, H. J., Choi, Y. M. and Ahn, T. S. Activation of macrophages and the intestinal immune system by an orally administered decoction from cultured mycelia of Cordyceps sinensis. Biosci. Biotechnol. Biochem. 66, 407-411 (2002).

Krammer, P. H. CD95's deadly mission in the immune system. Nature 407, 789-795 (2000).

Lamhamedi-Cherradi, S. E., Zheng, S. J., Maguschak, K. A., Peschon, J. and Chen, Y. H. Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL-/- mice. Nat. Immunol. 4, 255-260 (2003).

Lawen, A. Apoptosis-an introduction. Bioessays. 25, 888-96 (2003).

Lawen, A., Baker, M. A.and Malik, S. Apoptosis and redox homeostasis—On a possible mechanism of action of Bcl-2. Protoplasma. 205, 10-20 (1998).

Lee, H., Kim, Y. J., Kim, H. W., Lee, D. H., Sung, M. K.andPark, T.Induction of apoptosis by Cordyceps militaris through activation of caspase-3 in leukemia HL-60 cells. Biol. Pharm. Bull. 29, 670-674 (2006).

Lee, S. K. W., Wong, C. K., Kong, S. K., Leung, K. N., Lam, C. W. K. Immunomodulatory activities of HERBSnSENSES Cordyceps -- in vitro and in vivo studies. Immunopharmacol. Immunotoxicol. 28, 341-360 (2006).

Leverrier, Y. and Ridley, A. J. Apoptosis: caspases orchestrate the ROCK 'n' bleb. Nat. Cell Biol. 3, E91-3 (2001).

Li, S. P., Li, P., Dong, T. T. and Tsim, K. W. Anti-oxidation activity of different types of natural Cordyceps sinensis and cultured Cordyceps mycelia. Phytomedicine 8, 207-212 (2001).

Li, S. P., Zhang, G. H., Zeng, Q., Huang, Z. G., Wang, Y. T., Dong, T. T. and Tsim, K. W. Hypoglycemic activity of polysaccharide, with antioxidation, isolated from cultured Cordyceps mycelia. Phytomedicine 13, 428-433 (2006).

Liu, Y., Wu, C. and Li, C. Anti-oxidation of Paecilomyces Sinensis (S. Pnov.) Zhongguo. Zhong. Yao. Za. Zhi. 16, 240-2, 256 (1991).

Liu, X., Kim, C. N., Pohl, J. and Wang, X. Purification and characterization of an interleukin-1beta-converting enzyme family protease that activates cysteine protease P32 (CPP32). J. Biol. Chem. 271, 13371-13376 (1996).

Lo, H. C., Hsu, T. H., Tu, S. T. and Lin, K. C. Anti-hyperglycemic activity of natural and fermented Cordyceps sinensis in rats with diabetes induced by nicotinamide and streptozotocin. Am. J. Chin. Med. 34, 819-332 (2006).

Lo, H. C., Tu, S. T., Lin, K. C. and Lin, S. C. The anti-hyperglycemic activity of the fruiting body of Cordyceps in diabetic rats induced by nicotinamide and streptozotocin. Life Sci. 74, 2897-2908 (2004).

MacEwan, D. J. TNF receptor subtype signalling: differences and cellular consequences. Cell Signal 14, 477-492 (2002).

Mao, X. B. and Zhong, J. J. Optimization of carbon source and carbon/nitrogen ratio for cordycepin production by submerged cultivation of medicinal mushroom Cordyceps militaris. Process Biochem. 40, 1667-1672(2005).

Mao, X. B. and Zhong, J. J. Significant effect of NH4+ on cordycepin production by submerged cultivation of medicinal mushroom Cordyceps militaris. Enzyme and Microbol. Technol. 38 , 343–350 (2005).

Mehlen, P., Kretz-Remy, C., Preville, X. and Arrigo, A.P. Human hsp27, Drosophila hsp27 and human alphaB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFalpha-induced cell death. Embo. J. 15, 2695-2706 (1996).

Melino, G. The Sirens' song. Nature 412, 23 (2001).

Nakamura, K., Konoha, K., Yamaguchi, Y., Kagota, S., Shinozuka, K. and Kunitomo, M. Combined effects of Cordyceps sinensis and methotrexate on hematogenic lung metastasis in mice. Receptors Channels 9, 329-334 (2003).

Nakamura, K., Konoha, K., Yamaguchi, Y., Kagota, S., Shinozuka,K. and Kunitomo, M. Combined effects of Cordyceps sinensis and methotrexate on hematogenic lung metastasis in mice. Receptors Channels 9, 329-334 (2003).

Nestel, P. J. The role of antioxidants in preventing coronary disease.Suppl. Food Aust., 47: 28-29(1995).

Pan, G., Ni, J., Wei, Y. F., Yu, G., Gentz, R.and Dixit, V. M. An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277, 815-818 (1997).

Paolisso, G., D'Amore, A., Volpe, C.,Balbi, V., Saccomanno, F., Galzerano, D., Giugliano, D., Varricchio, M. and D'Onofrio, F. Evidence for a relationship between oxidative stress and insulin action in non-insulin-dependent (type II) diabetic patients. Metabolism. 43, 1426-1429 (1994).

Peluso, G. and Morrone, G. Antiphospholipid antibodies and recurrent abortions: possible pathogenetic role of annexin A5 investigated by confocal microscopy. Minerva. Ginecol. 59, 223-229 (2007).

possible mechanism of action of Bcl-2. Protoplasma 205,10–20(1998).
Ravagnan, L., Gurbuxani, S., Susin, S. A., Maisse, C., Daugas, E., Zamzami, N., Mak, T., Jaattela, M., Penninger, J. M., Garrido, C. and Kroemer, G.Heat-shock protein 70 antagonizes apoptosis-inducing factor. Nat. Cell Biol. 3, 839-843 (2001).

Sakamoto, H., Mashima, T., Yamamoto, K. and Tsuruo, T. Modulation of heat-shock protein 27 (Hsp27) anti-apoptotic activity by methylglyoxal modification. J. Biol. Chem. 277, 45770-45775 (2002).

Samali, A., Cai, J., Zhivotovsky, B., Jones, D.P. and Orrenius, S. Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells. Embo. J. 18, 2040-2048 (1999).

Shi, Y. Mechanisms of caspase activation and inhibition during apoptosis. Mol. Cell 9, 459-470 (2002).

Shigenaga, M. K. and Ames, B. N. Oxidants and mitogenesis as causes of mutation and cancer: the influence of diet. Basic. Life Sci. 61, 419-436 (1993).

Spector, A., Wang, G. M., Wang, R. R., Li, W. C. and Kleiman, N. J. A brief photochemically induced oxidative insult causes irreversible lens damage and cataract. II. Mechanism of action. Exp. Eye. Res. 60, 483-493 (1995).
Strasser, A., O'Connor, L. and Dixit, V. M. Apoptosis signaling. Annu. Rev. Biochem. 69, 217-245 (2000).

Studzinski GP. Apoptosis: A practical approach. Oxford, UK: Oxford University press, (1999)

Takayama, S., Reed, J.C. and Homma, S. Heat-shock proteins as regulators of apoptosis. Oncogene 22, 9041-7 (2003).

Thomadaki, H., Tsiapalis, C. M. and Scorilas, A. Polyadenylate polymerase modulations in human epithelioid cervix and breast cancer cell lines, treated with etoposide or cordycepin, follow cell cycle rather than apoptosis induction. Biol. Chem. 386, 471-480 (2005).

Thomas, M. J. The role of free radicals and antioxidants: how do we know that they are working? Crit. Rev. Food Sci. Nutr, 35: 21-39(1995).

Thornberry, N.A. and Lazebnik, Y. Caspases: enemies within. Science 281, 1312-1316 (1998).

Tindle, H.A., Davis, R.B., Phillips, R.S. and Eisenberg, D.M. Trends in use of complementary and alternative medicine by US adults: 1997-2002. Altern. Ther. Health Med. 11, 42-49 (2005).

Trump, B. F., Berezesky, I. K., Chang, S. H. and Phelps, P. C. The pathways of cell death: oncosis, apoptosis, and necrosis. Toxicol. Pathol. 25, 82-88 (1997).

Tsujimoto, Y. and Shimizu, S. The voltage-dependent anion channel: an essential player in apoptosis. Biochimie. 84, 187-193 (2002).

Van Parijs, L. and Abbas, A. K. Role of Fas-mediated cell death in the regulation of immune responses. Curr. Opin. Immunol. 8, 355-361 (1996).

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).

Wagner, J. R., Hu, C. C. and Ames, B. N. Endogenous oxidative damage of deoxycytidine in DNA. Proc. Natl. Acad. Sci. U. S. A.89, 3380-3384 (1992).

Wang, B. J., Won, S. J., Yu, Z. R. and Su, C. L. Free radical scavenging and apoptotic effects of Cordyceps sinensis fractionated by supercritical carbon dioxide. Food. Chem. Toxicol. 43, 543-552 (2005).

Waterhouse, N. J., Ricci, J. E. and Green, D. R. And all of a sudden it's over: mitochondrial outer-membrane permeabilization in apoptosis. Biochimie. 84, 113-121 (2002).

Wu, J. Y., Zhang, Q. X. and Leung, P. H. Inhibitory effects of ethyl acetate extract of Cordyceps sinensis mycelium on various cancer cells in culture and B16 melanoma in C57BL/6 mice. Phytomedicine (2006).

Wu, W. C., Hsiao, J. R., Lian, Y. Y., Lin, C. Y. and Huang, B. M. The apoptotic effect of cordycepin on human OEC-M1 oral cancer cell line. Cancer Chemother. Pharmacol. (2006).

Yamaguchi, N. et al. Augmentation of various immune reactivities of tumor-bearing hosts with an extract of Cordyceps sinensis. Biotherapy 2, 199-205 (1990).

Yamaguchi, Y., Kagota, S., Nakamura, K., Shinozuka, K. and Kunitomo, M. Antioxidant activity of the extracts from fruiting bodies of cultured Cordyceps sinensis. Phytother. Res. 14, 647-649 (2000).

Yoshikawa, N., Nakamura, K., Yamaguchi, Y., Kagota, S., Shinozuka, K. andKunitomo, M. Antitumour activity of cordycepin in mice. Clin. Exp. Pharmacol. Physiol., 31 Suppl 2, S51-53 (2004).

Zhang, G., Huang, Y., Bian, Y., Wong, J. H., Ng, T. B. and Wang, H. Hypoglycemic activity of the fungi Cordyceps militaris, Cordyceps sinensis, Tricholoma mongolicum, and Omphalia lapidescens in streptozotocin-induced diabetic rats. Appl. Microbiol. Biotechnol. 72, 1152-1156 (2006).

Zhang, Q. X. and Wu, J. Y. Cordyceps sinensis mycelium extract induces human premyelocytic leukemia cell apoptosis through mitochondrion pathway. Exp. Biol. Med. (Maywood) 232, 52-57 (2007).

Zhang, X., Liu, Y. K., Zheng, Q., Shen, W. and Shen, D. M. Influence of Cordyceps sinensis on pancreatic islet beta cells in rats with experimental liver fibrogenesis. Zhonghua. Gan. Zang. Bing. Za. Zhi. 11, 93-94 (2003).

Zhao, C. S. et al. CordyMax Cs-4 improves glucose metabolism and increases insulin sensitivity in normal rats. J. Altern. Complement Med. 8, 309-314 (2002).
Zuckerman, S. H., Evans, G. F., Snyder, Y. M. and Roeder, W. D. Endotoxin-macrophage interaction: post-translational regulation of tumor necrosis factor expression. J. Immunol. 143, 1223-7 (1989).
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