植物内生真菌抗肿瘤活性物质的研究
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摘要
植物内生真菌是指生活在植物组织体内的一类并不引起明显病害症状的真菌，包括了那些在其生活史中的某一阶段营表生的腐生菌，对宿主暂时没有伤害的潜伏性病原菌(Latent pathogens)和菌根菌(mycorhizafungi)。它是一个庞大的特殊的真菌类群，几乎所有的植物组织中都发现有内生真菌的存在。研究表明，在某些药物植物(如红豆杉)中，存在一些能够产生与宿主相同代谢产物(如紫杉醇)的内生真菌；而且由于真菌与植物之间长期的相互作用和共同进化，其代谢产物十分丰富，包括杀虫、抗菌和抗肿瘤等活性物质。因此，植物内生真菌现己成为寻找抗肿瘤药物的重要来源。
我国药用植物资源十分丰富，对其内生真菌的研究将有利于我国微生物药物的开发和珍稀植物资源的保护。本文以福建省几种珍稀药用植物为对象，研究其内生真菌抗肿瘤活性，目的在于确定抗肿瘤活性菌株的生态分布及其抗肿瘤特性，从而为植物—真菌生态关系的研究以及植物内生真菌资源的利用提供依据。
从福建武夷山、三明沙县等地区的南方红豆杉、香榧和三尖杉的树皮中共分离得到172株内生真菌。采用细胞毒筛选模型(MTT法)对这些内生真菌发酵液的抗肿瘤活性进行了检测。结果表明，共有25株内生真菌(占总供测菌株的14.5％)的发酵液对KB或HL-60细胞生长有明显的抑制作用(ID50≤1：50)。红豆杉、香榧和三尖杉内生真菌抗肿瘤活性菌株各占供测菌株的19.6％、8.6％和3.3％。抗肿瘤活性菌株主要分布于拟青霉属(28％)和头孢霉属(24％)等8个属中，同属真菌的抗肿瘤活性也有很大的差异。内生真菌种属和生物活性的多样性为寻找抗肿瘤活性代谢物质奠定了基础。
对两株分离自红豆杉和香榧的抗肿瘤高活性菌株W-TF5和H-036的抗肿瘤活性物质作了进一步的研究。采用TLC、UV、HPLC、MS等理化方法和MTT以及细胞外和细胞内微管聚合等生物实验手段证实了W-TF5发酵液有机抽提物中存在抗肿瘤药物紫杉醇；采用柱层析和重结晶等方法从W-TF5发酵液中分离到另一种抗肿瘤活性物质的结晶，X-Ray单晶衍射、IR、MS以及NMR等数据表明该晶体是一种11元环松胞菌素——松胞菌素D(Cytochalasin D，CytD)，首次确定了松胞菌素D的晶体结构。
H-036发酵液对HL60、KB、Hela、SPC-A-1和MCF-7细胞都具有
王建锋博士论文 摘 要、11．
很强的细胞毒作用，将其发酵液用乙酸乙酯抽提浓缩后，用甲醇、丙酮等
溶剂反复重结晶，即可得到无色纯净的柱状晶体。采用XRay单晶衍射、
IR以及NMR等手段确定了该晶体的是一种大环内酯类物质—一布雷菲德
菌素 A（Brefe旧in A，BFA）。
本文工作证实了南方红豆杉、香皿和三尖杉中存在着丰富的植物内生
真菌资源，种属多样。抗肿瘤活性菌株W－TFS除了产生紫杉醇外，还可
产生 CytD，经鉴定为一种瘤座抱（Tubercularia sp、X 这是首次从红豆杉
类植物中分离到瘤座抱属真菌，是一株紫杉醇和松胞菌素新的产生菌。
Ho36可产生 BFA（产量 31 00mglL发酵液人 经鉴定为一种拟青霉
（Paecilomyces sp．L是一株布雷菲德菌素新的产生菌。这些结果表明药
用植物内生真菌是研究和开发抗肿瘤微生物药物的宝贵资源。
本文还对分离到的CytD和BFA对肿瘤细胞的作用作了初步的探讨。
采用MTT和贴壁集落等方法检测了CytD和BFA对HL60、KB等肿瘤细
胞的抑制作用，并采用流式细胞检测法和激光共聚焦扫描形态观察法研究
了CytD和8＊A诱导细胞凋亡的作用。结果表明，Cy旧对H＊0、＊B、
＊＊a、＊C＊7和即C－入1细胞的忆5。分别为25o、25o、250、500、10o
nglml；BFA的细胞毒作用要比 CytD强，对这些细胞的 IC幼分别为 15、
10、3刀、2石、2刀 nglml。CytD能够诱导 HL60和 KB细胞 GZIM期阻滞
和细胞凋亡：经oytD处理的K日细胞在6 h 内就出现起泡现象〔0dD
b旧bbing），在 24 h后 GZIM 期阻滞至达最高峰（18％上升至 40％），48 h
后 BC卜2的表达明显下降，大量细胞凋亡（4．8％上升到 55％）。提示微丝
系统对细胞信号的传导具有重要作用，对微丝的破坏，可能会诱导细胞凋
亡。BFA能够诱导HL60及KB细胞的G0lGI期阻滞和细胞凋亡。BFA处
理 KB细胞 24 h后，细胞不能由 G。期进入 S期，导致 G。IG；期阻滞，此
时只有个别的细胞发生凋亡，但 48 h后细胞即大量凋亡，并伴随着 BC12
的磷酸化。
Endophytic fungi are the microbes associated with living tissue of plants without causing any noticeable symptoms of disease. They constitute a large, special fungal group, and they are to be found in all or almost all plants. It's reported that some endophytic fungi could produce the same metabolite as that produced by their hosts. For example, some endopytic fungi isolated from Taxus sp. could produce taxol, one of most important antitumor drugs. Moreover, the secondary metabolites of endophytic fungi are abundant, including insecticidal, antimicrobic and antitumor agents. Therefore, endophytic fungi have become a new promising source for screening antitumor drugs.
China has very rich pharmaceutical plants resources. Studies on endophytic fungi will promote the development of microbial medicine and help the protection of the valuable and rare plants. We have studied the antitumor activities of the endophytic fungi of several pharmaceutical plants in Fujian province in order to find new antitumor drugs.
Altogether there were 172 strains of endophytic fungi isolated from the bark of three plants from Wuyi Mountain and Sanming County in Fujian province: Taxus mairei, Torreya grandis and Cephalataxus fortunei. The antitumor activities of the fermentation broths of these endophytic fungi were tested by MTT method. The result shows that 25 fermentation broths (about 14.5% of the total strains isolated) show noticeable growth inhibition against KB and HL6O tumor cells. The strains with antitumor activity in three plants, T. makei, T. grandis, C. fortunei account for 19.6%, 8.6%, 3.3% respectively among the total strains isolated. The strains with antitumor activity can be grouped into 8 genera by conventional identification. Paecilomyces (28%) and Cephalosporium (24%) were the main genera among the strains identified with antitumor activity. Even in the same genus, the antitumor activities show obvious difference. The diversity of genera and antitumor activities provides us with the possibility of searching antitumor metabolites.
We further studied the antitumor metabolites of two strains with
high antitumor activity, W-TF5 and H-036, which respectively isolated from T mairei and T grandis. Using TLC, UV, HPLC, MS, MIT, Tubulin Assembly methods, we verified that W-TF5 could produce taxol. From organic extract of W-TF5 fermentation broth, we also isolated another antitumor compound by column chromatography and recrystal methods, which was identified as Cytochalsin D (CytD) by X-Ray single crystal diffraction, IR, MS and NMR methods. Moreover, the X-Ray crystal structure of CytD was determined for the first time in the world.
The fermentation broth of H-036 has a strong cytotoxicity on HL6O. KB. Hela~ SPC-A-1 and MCF-7 tumor cells. After the broth was extracted with ethyl acetate and condensed, and recrystalized in methanol and acetone repeatedly, a kind of colorless, pure columner shaped crystal was obtained, which identified as Brefeldin A (BFA) by X-Ray single crystal diffraction, lR and NMR methods.
Our studies show that endophytic fungi are abundant in T mairei, T grandis and C. fortunei with great diversity. Strain W-1F5, identified as a Tubercularia sp., can produce both Taxol and CytD. This is the first time that finds Tubercularia sp. isolated from Taxus sp., and strain W-TF5 has been found as a new taxol and CytD-producing fungus. Strain H-036, identified as a Paediomyces sp., can produce BFA with high production (~10Omg/L), which is a new BFA-producing fungus. These results indicate that studies on endophytic fungi of pharmaceutical plants are beneficial to develop new microbial medicine.
We also primarily studied the effects of CytD and BFA on tumor cell. CytD shows cytotoxicity on all tested tumor cell lines (HL60~ KB~ Hela. MCF-7 and Spc-A-1) with 1C50 ranging from 100 ng/ml to 500 ng/ml. BFA has stronger cytotoxicity than CytD with IC50 ranging from 2.0 ng/ml to 15 ng/ml. CytD can induce G2IM inhibition and apoptosis of HL6O and KB cells. After treated with CytD, KB cells appeared cell b
我国药用植物资源十分丰富，对其内生真菌的研究将有利于我国微生物药物的开发和珍稀植物资源的保护。本文以福建省几种珍稀药用植物为对象，研究其内生真菌抗肿瘤活性，目的在于确定抗肿瘤活性菌株的生态分布及其抗肿瘤特性，从而为植物—真菌生态关系的研究以及植物内生真菌资源的利用提供依据。
从福建武夷山、三明沙县等地区的南方红豆杉、香榧和三尖杉的树皮中共分离得到172株内生真菌。采用细胞毒筛选模型(MTT法)对这些内生真菌发酵液的抗肿瘤活性进行了检测。结果表明，共有25株内生真菌(占总供测菌株的14.5％)的发酵液对KB或HL-60细胞生长有明显的抑制作用(ID50≤1：50)。红豆杉、香榧和三尖杉内生真菌抗肿瘤活性菌株各占供测菌株的19.6％、8.6％和3.3％。抗肿瘤活性菌株主要分布于拟青霉属(28％)和头孢霉属(24％)等8个属中，同属真菌的抗肿瘤活性也有很大的差异。内生真菌种属和生物活性的多样性为寻找抗肿瘤活性代谢物质奠定了基础。
对两株分离自红豆杉和香榧的抗肿瘤高活性菌株W-TF5和H-036的抗肿瘤活性物质作了进一步的研究。采用TLC、UV、HPLC、MS等理化方法和MTT以及细胞外和细胞内微管聚合等生物实验手段证实了W-TF5发酵液有机抽提物中存在抗肿瘤药物紫杉醇；采用柱层析和重结晶等方法从W-TF5发酵液中分离到另一种抗肿瘤活性物质的结晶，X-Ray单晶衍射、IR、MS以及NMR等数据表明该晶体是一种11元环松胞菌素——松胞菌素D(Cytochalasin D，CytD)，首次确定了松胞菌素D的晶体结构。
H-036发酵液对HL60、KB、Hela、SPC-A-1和MCF-7细胞都具有
王建锋博士论文 摘 要、11．
很强的细胞毒作用，将其发酵液用乙酸乙酯抽提浓缩后，用甲醇、丙酮等
溶剂反复重结晶，即可得到无色纯净的柱状晶体。采用XRay单晶衍射、
IR以及NMR等手段确定了该晶体的是一种大环内酯类物质—一布雷菲德
菌素 A（Brefe旧in A，BFA）。
本文工作证实了南方红豆杉、香皿和三尖杉中存在着丰富的植物内生
真菌资源，种属多样。抗肿瘤活性菌株W－TFS除了产生紫杉醇外，还可
产生 CytD，经鉴定为一种瘤座抱（Tubercularia sp、X 这是首次从红豆杉
类植物中分离到瘤座抱属真菌，是一株紫杉醇和松胞菌素新的产生菌。
Ho36可产生 BFA（产量 31 00mglL发酵液人 经鉴定为一种拟青霉
（Paecilomyces sp．L是一株布雷菲德菌素新的产生菌。这些结果表明药
用植物内生真菌是研究和开发抗肿瘤微生物药物的宝贵资源。
本文还对分离到的CytD和BFA对肿瘤细胞的作用作了初步的探讨。
采用MTT和贴壁集落等方法检测了CytD和BFA对HL60、KB等肿瘤细
胞的抑制作用，并采用流式细胞检测法和激光共聚焦扫描形态观察法研究
了CytD和8＊A诱导细胞凋亡的作用。结果表明，Cy旧对H＊0、＊B、
＊＊a、＊C＊7和即C－入1细胞的忆5。分别为25o、25o、250、500、10o
nglml；BFA的细胞毒作用要比 CytD强，对这些细胞的 IC幼分别为 15、
10、3刀、2石、2刀 nglml。CytD能够诱导 HL60和 KB细胞 GZIM期阻滞
和细胞凋亡：经oytD处理的K日细胞在6 h 内就出现起泡现象〔0dD
b旧bbing），在 24 h后 GZIM 期阻滞至达最高峰（18％上升至 40％），48 h
后 BC卜2的表达明显下降，大量细胞凋亡（4．8％上升到 55％）。提示微丝
系统对细胞信号的传导具有重要作用，对微丝的破坏，可能会诱导细胞凋
亡。BFA能够诱导HL60及KB细胞的G0lGI期阻滞和细胞凋亡。BFA处
理 KB细胞 24 h后，细胞不能由 G。期进入 S期，导致 G。IG；期阻滞，此
时只有个别的细胞发生凋亡，但 48 h后细胞即大量凋亡，并伴随着 BC12
的磷酸化。
Endophytic fungi are the microbes associated with living tissue of plants without causing any noticeable symptoms of disease. They constitute a large, special fungal group, and they are to be found in all or almost all plants. It's reported that some endophytic fungi could produce the same metabolite as that produced by their hosts. For example, some endopytic fungi isolated from Taxus sp. could produce taxol, one of most important antitumor drugs. Moreover, the secondary metabolites of endophytic fungi are abundant, including insecticidal, antimicrobic and antitumor agents. Therefore, endophytic fungi have become a new promising source for screening antitumor drugs.
China has very rich pharmaceutical plants resources. Studies on endophytic fungi will promote the development of microbial medicine and help the protection of the valuable and rare plants. We have studied the antitumor activities of the endophytic fungi of several pharmaceutical plants in Fujian province in order to find new antitumor drugs.
Altogether there were 172 strains of endophytic fungi isolated from the bark of three plants from Wuyi Mountain and Sanming County in Fujian province: Taxus mairei, Torreya grandis and Cephalataxus fortunei. The antitumor activities of the fermentation broths of these endophytic fungi were tested by MTT method. The result shows that 25 fermentation broths (about 14.5% of the total strains isolated) show noticeable growth inhibition against KB and HL6O tumor cells. The strains with antitumor activity in three plants, T. makei, T. grandis, C. fortunei account for 19.6%, 8.6%, 3.3% respectively among the total strains isolated. The strains with antitumor activity can be grouped into 8 genera by conventional identification. Paecilomyces (28%) and Cephalosporium (24%) were the main genera among the strains identified with antitumor activity. Even in the same genus, the antitumor activities show obvious difference. The diversity of genera and antitumor activities provides us with the possibility of searching antitumor metabolites.
We further studied the antitumor metabolites of two strains with
high antitumor activity, W-TF5 and H-036, which respectively isolated from T mairei and T grandis. Using TLC, UV, HPLC, MS, MIT, Tubulin Assembly methods, we verified that W-TF5 could produce taxol. From organic extract of W-TF5 fermentation broth, we also isolated another antitumor compound by column chromatography and recrystal methods, which was identified as Cytochalsin D (CytD) by X-Ray single crystal diffraction, IR, MS and NMR methods. Moreover, the X-Ray crystal structure of CytD was determined for the first time in the world.
The fermentation broth of H-036 has a strong cytotoxicity on HL6O. KB. Hela~ SPC-A-1 and MCF-7 tumor cells. After the broth was extracted with ethyl acetate and condensed, and recrystalized in methanol and acetone repeatedly, a kind of colorless, pure columner shaped crystal was obtained, which identified as Brefeldin A (BFA) by X-Ray single crystal diffraction, lR and NMR methods.
Our studies show that endophytic fungi are abundant in T mairei, T grandis and C. fortunei with great diversity. Strain W-1F5, identified as a Tubercularia sp., can produce both Taxol and CytD. This is the first time that finds Tubercularia sp. isolated from Taxus sp., and strain W-TF5 has been found as a new taxol and CytD-producing fungus. Strain H-036, identified as a Paediomyces sp., can produce BFA with high production (~10Omg/L), which is a new BFA-producing fungus. These results indicate that studies on endophytic fungi of pharmaceutical plants are beneficial to develop new microbial medicine.
We also primarily studied the effects of CytD and BFA on tumor cell. CytD shows cytotoxicity on all tested tumor cell lines (HL60~ KB~ Hela. MCF-7 and Spc-A-1) with 1C50 ranging from 100 ng/ml to 500 ng/ml. BFA has stronger cytotoxicity than CytD with IC50 ranging from 2.0 ng/ml to 15 ng/ml. CytD can induce G2IM inhibition and apoptosis of HL6O and KB cells. After treated with CytD, KB cells appeared cell b
引文
1． Agarwala SP, Sagar SK, Sehgal SS (1999) Use of mycelial suspension and metabolites of Paecilomyces lilacinus (Fungi: Hyphomycetes) in control of Aedes aegypti larvae. J Commun Dis, 31(3) :193-6．
2． Ainsworth GC,Sparrow F K and Sussman AS (1973) The fungi, an advanced treatise. Vol. IVA, A taxonomic review with keys: Ascomycetes and fungi imperfecti. Academic press New York and London. 05, 428, 445, 514．
3． Albertsson J, Fex T, Svensson C (1981) X-ray study of Cytochalasin M, a secondary metabolite from the fungus Chalara microspora. Acta Chem.Scand.Ser.A, 35, 707．
4． Aldridge DC and Turner WB (1969) The identity of zygosporin A and cytochalasin D. J. Antibiotic. 170．
5． Alvarez C, Sztul ES (1999) Brefeldin A (BFA) disrupts the organization of the microtubule and the actin cytoskeletons. European Journal of Cell Biology. 78(1) : 1-14．
6． Bacon CW (1993) Antibiotic stress tolerances (moisture, nutrients) and photosynthesis in endophyte infected tall fescue. Agric Ecosystens Environ, 44:123-141．
7． Bacon CW, Lyons PC, Porter JK Robbins JD (1986) Ergot toxicity from endophyte-infected grasses: a review. Agron J, 78: 106-116．
8． Barnett HL and Hunter BB (1977) Illustrated genera of imperfect fungi. (Third edition, Chines version), China scientific press. 144-145．
9． Basualdo JA, Ciarmela ML, Sarmiento PL, Minvielle MC (2000) Biological activity of Paecilomyces genus against Toxocara canis eggs. Parasitology Research, 86(10) : 854-859．
10． Bellag DM, McQuency PA, Zhu J, Hensens O, Konpal L, Liesch J, Geetz M, Larariaes E and Woods CM (1995) Epothilopes, A new class of microtubule-stablizing agents with a taxol-like mechanism of action. Cancer Res. 55, 2325-2333．
11 Beno MA and Christoph GG (1976) X-ray crystal structure of Cytochalasin H, a potent new [11] cytochalasan toxin, Chem. Comm. 344-345． ,
12． Beno MA, Cox RH, Wells JM, Cole RJ, Kirksey JW (1977) Structure of a new [11] cytochalasin, cytochalasin H or Kodo-cytochalasin-1． J.Am.Chem.Soc. 99: 4123-4124．
13． Betina V (1969) Effect of the macrolide antibiotic, cyanein on Hela cell growth and metabolism. Neoplasma, 16:23-32．
14． Betina V (1992) Biological effects of the antibiotic brefeldin A (decumbin,
cyanein, ascotoxin, synergisidin): a etrospec-tive, Folia Microbiol. 37: 3-11．
15． Betina V, Drobnica L, Nemec P and Zemanova M (1964) Study of the antifungal activity of the antibiotic cyanein. J. Antibiotics Ser. A, 17: 353-357．
16． Betina V, Nemec P, Dobias J, and Barath Z (1966) Cyanein, a new antibiotic from Peniciltium cyaneum. Folia Microbiol. (Praha) 7:353-357．
17． Boiler T (1995) Chemoperception of microbial signal in plant cells. Annu Rev Physiol Plant Biol, 46: 189-214．
18． Buchi G, Kitaura Y and Yuan SS (1973) Structure of cytochalasin E, a toxic metabolite of Aspergillus clavatus, J. Am Chem. Soc. 96(16) , 5423-5425．
19． BuLock JD, and Clay PT (1969) ,Fatty acid cyclization in the biosynthesis of brefeldin A; a new route to some fungal metabolites. Chem. Commun, 237-238．
20． Buolamwini JK (1999) Novel anticancer drug discovery, Current Opinion in Chemical Biology, 3: 500-509．
21． Cameron AF, Freer AA, Hesp B, Strawson CJ (1974) Isolation, and crystal and molecular structure of cytochalasin G: an [11] cytochalasan containing an indole group J.Chem.Soc.,Perkin Trans.2, 1741．
22． Carolin DS, Zoe AS, Deborah M, Luo JT (1998) Mitotic phosphorylation of Bcl-2 during Normal cell cycle progression and taxol-induced growth arrest. J. Biol. Chem., 273(46) : 30777-30784．
23． Carroll G (1988) Fungal endophytes in stems and leaves: from latent pathogen to mutualistic symbiont. Ecology, 69: 2-9
24． Carter SB (1967) Effects of cytochalasins on mammalian cells. Nature, 213: 261-264．
25． Chapman JR, Tazaki H, Mallouh C, Konno S (1999) Brefeldin A-induced apoptosis in prostatic cancer DU-145 cells: a possible p53-independent death pathway. BJU Int, 83(6) :703-8．
26． Chardin P. and McCormick F. (1999) , Brefeldin A: The advantage of being uncompetitive. Cell 97:153-155．
27． Cho SW, Kim N, Choi MU, Shin W (2001) Structure of aspergillopepsin I from Aspergillus phoenicis:variations of the SV-S2' subsite in aspartic proteinases. Acta Crystallogr D Biol Crystallogr, 57(Pt 7) :948-56
28． Christen AA, Gibson DM, Bland JB (1991) Production of taxol or taxol-like compounds in cell culture. US patent, 5, 019, 504
29． Clay K (1987) Effects of fungal endophytes on the seed and seedling biology of Lolium perenne and Festuca arundinacea. Cecologia, 73: 358-362．
30． Clay K (1988) Fungal endophytes of grasses: a defensive mutualism. Ecology, 69: 10-16．
31． Clay K (1990) Fungal endophyte of grasses. Annu Rev Ecol Syst, 21: 257-297．
32． Cline SD, Coscia CJ (1988) Stimulation of sanguinary inproduction by combined fungal elicitation and hormonal deprivation in cell suspension cultures of Papaver bracteatum. Plant Physiol, 86: 161-165．
33． Cooper JA (1987) Effects of Cytochalasin and phalloidin on actin. J.cell Biol..105． 1473-1478．
34． Daniel IO, Loy EV (1995) Proteolysis of p6． 9 induced by cytochalasin D in Autographa californica M nuclear ployhedrosis virus-infected cells, virology, 207: 1-11．
35． Daniel MB, McQueney PA, Zhu J, Hensens O, Konpal L, Liesch J, Geetz M, Larariaes, Woods CM (1995) Epothilopes, A new class of microtubule stablizing agents with a taxol-like mechanism of action. Cancer Res., 55: 2325-2333．
36． Demain AL, Hunt NA, Malik V, Kobbe B, Hawkins H, Matsuo K,Wogan GN (1976) Improved procedure for production of cytochalasin E and tremorgenic mycotoxins by Aspergillus clavatus. Appl Environ Microbiol, 31(1) :138-40．
37． Denis JN, Green AE, Gerenard D (1998) A highly efficient, practical approach to natural taxol. J Am Chem Soc, 110 (17) : 5917-5919．
38． Douros J, Suffness M, (1982) . ,9(1) : 17-24．
39． Edward, HK, Kevin J, Volk SE, Hill. (1994) Profiling taxanes in Taxus extracts using LC/MS and LC/MS/MS techniques. J. Natural products. 57, 1391-1403．
40． Eilert U, Kurz WG , Constabel F (1984) Stimulation of sanguinarine accumulation in vapaver somniferum cell cultures by fungal elicitors.J Plant Physiol, 119: 65-76．
41． Entwistle ID, Howard CC, Johnstone RAW (1974) Isolation of brefeldin A from Phyllosticta medicaginis, Phyto-chemistry, 13 173-174．
42． Evidente A, Capasso R, Vurro M, and Bottalica A (1996) Cytochalasin W, a new 24-oxa[14] cytochalasan from Phoma exigua var Nat. Toxins, 4(2) :53-57
43． Evidente A., Lanzetta R., Capasso R., Vurro M.and Bottalico A (1992) Cytochalasin U and V, two new cytochalasans, from Phoma exigua var. heteromorpha, Tetrahedron, 48(30) , 6317-6324．
44． Fex T (1981) Structures of cytochalasin K, L, and M, isolated from Chalara microspora. Tetrahedron Lett., 22(28) ,2703-2706．
45． Fisher P J, Petrini O, Sutton B C (1993) A comparative study of fungal endophytes in leaves, xylem and bark of Eucalyptus nitens in Australia and England. Sydowia, 45: 338-345．
46． Fujii Y, Tani H, Ichinoe M, and Nakajima H (2000) Zygosporin D and two new cytochalasins produced by the fungus Metrarrhizium anisopliae, J. Nat. Prod., 63:132-135．
47． Funk CR, White RH, Breen JP (1993) Importance of Acremvnium endophytes in turf-grass breeding and management. Agric Ecosystem Environ, 44: 215-232．
48． Goddete DW, and Frieden C (1986a) The Kinetics of cytochalasin D binding to monomeric actin. J. Boil. Chem., 261:15970-15973．
49． Goddete DW, and Frieden C (1986b) Actin polymerization, the mechanism of action of cytochalasin D, J. Boil. Chem., 261:15973-15980．
50． Graf W, Robert JL, Vederas JC, Tamm C, Solomon PH, Miura I, Nakanishi K (1974) Biosynthesis of the cytochalsans (Part III. 13C-NMR of cytochalasin B (Phomin) and cytochalsin D incorporation of [1-13C]-and [2-13C]-sodium acetate). Helv. Chem. Ada, 57(6) :1801-1815．
51． Griffin JF, Rampal AL, Jung CY (1980) The structure of cytochalsin A. Am.Cryst.Assoc.Ser.2, 7-13．
52． Guo H, Tittle TV, Allen H, Maziarz RT (1998) Brefeldin A-mediated apoptosis requires the activation of caspases and is inhibited by Bcl-2． Exp Cell Res, 245(1) :57-68．
53． Guptars (1987) Synthesis and biological activities of c4 esters of 4' demethylepipodophyllotoxin. Anticancer Drug Design, 2:13-15．
54． Hacki J, Egger L, Monney L, Conus S, Rosse T, Fellay I, Borner C (2000) Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2． Oncogene, 19(19) :2286-95．
55． Harri E, Loeffier W, Sigg HP, Stahelin H and Tamm C (1963) Ober die isolierung neuer stoffwechselprodukte aus Penicillium brefeldianum DODGE, Helv. Chem. Acta, 46(6) : 1235-1243．
56． Harris JP, Mantle PG (2001) Biosynthesis of by Aspergillus ochraceus. Phytochemistry, 57(2) : 165-9．
57． Hawksworth DL, Sutton BC and Ainsworth GC (1983) Dictionary of the fungi, (Seventh Edition). Common Wealth Mycological Institute, Kew, Surrey. 1-500．
58． Hawksworth, DL (1991) The fungal dimension of biodiversity: magnitude, significance, and conservation. Mycol. Res, 95:641-655．
59． Helms JB and Rothman JE (1992) Inhibition by brefeldin A of a goldi membrane enzyme that catalyses exchange of guanine mucleotide bound to ARF. Nature, 360:352-353．
60． Hezari M and Croteau R (1997) Taxol biosynthesis: an update. Planta Medica 63:291-295．
61． Hinton DM, Bacon CM (1985) The distribution and ultrastructure of endophyte of toxic tall fescue. Can J Bot. 63: 36-42．
62． Huang KC, Hwang YY, Hwu L, Lin A (1997) Characterization of a new ribotoxin gene (c-sar) from Aspergillus clavatus. Toxicon. 35 (3) : 383-92．
63． Hugh R, Pelham B (1991) Multiple targets for brefeldin A. Cell, 67:449-451．
64． Johnson MC, Anderson RL, Krysolo RJ, Siegel MR (1983) Sampling procedure for determining endophyte content in tall fescue seed lots by ELISA. Phytopathology, 73: 1046-1049．
65． Johnson MC, Pirone TP, Siegel MR, Varney DR (1982) Detection of Epichloe typhina in tall fescue by means of enzyme-linked immunosorbent assay. Phytopathology, 72: 647-650．
66． Jordan MA, Toso RJ, Thrower D and Wilson L (1993) Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concertrations. Proc. Natl. Acad. Sci. USA, 90:9552-9556．
67． Kakeya H, Morishita M, Onozawa C, Usami R, Horikoshi K, Kimura K, Yoshihama M and Osada H (1997) RKS-1778, a new mammalian cell-cycle inhibitor and a key intermediate of the [11] cytochalasin group. J. Nat. Prod. 60,669-672．
68． Katagiri K and Matsuura S (1971) Antitumor activity of cytochalasin D. J. Antibiotics, 24(10) : 722-723
69． Kwong YL, Au WY, Chim CS, Pang A, Suen C, Liang R. (2001) Arsenic trioxide-and idarubicin-induced remissions in relapsed acute promyelocytic leukaemia:clinicopathological and molecular features of a pilot study. Am J Hematol., 66(4) :274-9．
70． Li JY, Harper JK, Grant DM, Tombe BO, Bashyal B, Hess WM, Strobel GA (2001 A) Ambuic acid, a highly functionalized cyclohexenone with antifungal activity from Pestalotiopsis spp. and Monochaetia sp.. Phytochemistry, 56: 463-468．
71． Li JY, Sidhu RS, Bollon A,Strobel GA (1998B) Stimulation of taxol production in liquid cultures of Pestalotiopsis microspora. Mycol Res, 102(4) : 461-464．
72． Li JY, Sidhu RS, Ford EJ, Long DM, Hess WM and Strobel GA (1998A) The induction of taxol production in the endophytic fungus-Periconia sp. from Torreya grandifolia. J. Industrial Microbiology & biotechnology, 20(5) : 259-264．
73． Li JY, Strobel GA (2001B) Jesterone and hydroxy-jesterone antioomycete cyclohexenone epoxides from the endophytic fungus Pestalotiopsis jesteri. Phytochemistry, 57: 261-265．
74． Lin DC, Tobin KD, Grumet M and Lin S (1980) Cytochalasins inhibit nuclei-induced actin polymerization by blocking filament elongation. J. Cell Biol., 84:455-460．
75． Lopez-Diaz TM, Flannigan B. ( 1997 ) Production of patulin and cytochalasin E by Aspergillus clavatus during malting of barley and wheat. Int J Food Microbiol, 35(2) :129-36．
76． Lu H, Zou WX, Meng JC, Hu J, Tan RX (2000) New bioactive metabolites produced by Colletotrichum sp., an endophytic fungus in Artemisia annua. Plant Science, 151(1) : 67-73．
77． Mabuni CT, Garlaschelli L, Ellison RA, Hutchinson CR (1977) Biosynthetic origin of the oxygen atoms in the C15 macrolide antibiotic brefeldin A J Am Chem Soc, 99(23) : 7718-20．
78． Maccotta A, Vaiensin G, Gaggelli N, Gaggelli E (1993) The conformation of cytochalasin D in DMSO solution frm 1H and 13C NMR relaxation rates. J. Chem. Soc. Perkin Trans.2, 729-732．
79． Manti L, Bowen ID, Mason MD, Court JB (2000) Apoptosis is a mode of cell death in the polykaryon-forming unit assay. Cell Biol Int 24(7) :415-25
80． Marks S, Clay K (1996) Physiological responses of Festuca arundinacea to fungal endophyte infection. New Phytol, 133: 727-733．
81． Mclaughlin G, Sim GA, Kiechel JR and Tamm C (1970) Chem. Comm., 1398-1399．
82． McMillan JA, Chiang CC, Greensley MK, Paul IC, Patwardhan SA, Dev S, Beno MA, Christoph GG (1977) X-ray crystal and molecular structure of kodo-cytochalasin-1, Chem.Comm., 105-106．
83． Miata H and Matsumoto M (1970) Studies of the metabolites of Zygosporium masonu, Part I.Structure of zygosporin A., J. Chem. Soc.(C), 38-47．
84． Munshi NC. (2001) Arsenic trioxide: an emerging therapy for multiple myeloma. Oncologist.Suppl, 2:17-21．
85． Murgo AJ (2001) Clinical trials of arsenic trioxide in hematologic and solid tumors: overview of the National Cancer Institute Cooperative Research and Development Studies. Oncologist. Suppl 2:22-8．
86． Nagasawa H, Nagura R, Mohamad SB, Uto Y, Zhu JW, Tsukuda T, Hashimoto T, Asakawa Y. Hori H (2000) , Apoptosis induction oin HCT116 cells by cytochalasin isolated from the fungus Daldinia vernicosa, Phytomedicine, 6(6) : 403-409．
87． Nicolaou KC, Yang Z, Liu JJ, Ueno H, Nantermet PG, Guy RK, Claiborne CF, Renaud J, Couladouros EA, Paulvannan K, Sorense EJ. (1994) Total xynthesis of taxol. Nature. 367: 630-634．
88． Nicole B, Nicole M (1999) Cell biology of plant immunization against
microbial infection: The potential of induced resistance in controlling plant diseases. Plant Physiol Biochem, 37(10) : 703-719
89． Nilanonta C,Isaka M, Kittakoop P, Palittapongarnpim P, Kamchonwongpaisan S, Pittayakhajonwut D, Tanticharoen M, Thebtaranonth Y (2000) Antimycobacterial and antiplasmodial cyclodepsipeptides from the insect pathogenic fungus Paecilomyces tenuipes BCC1614． Planta Medica, 66(8) : 756-758．
90． Nisbet LJ, Fox FM (1991) The importance of microbiodiversity to biotechnology. Hawksworth D L (ed) The Biodiversity of Microorganisms and Invertebrates: Its Role in Sustainable Agriculture, 229-244．
91． Noh MJ, Yang JG, Kim KS, Yoon YM, Kang KA, Han HY, Shim SB, Park HJ (1999) Isolation of a novel microorganism, Pestalotia heterocornis, producing paclitaxel. Biotechnology And Bioengineering, 64(5) : 620-623．
92． Ohmori H, Toyama Su and Toyama Sa (1992) Direct proof that the primary site of action of cytochalasin on cell motility processes is actin, J. cell Biol. 116: 933-941．
93． Otmar S, Jochen B (1987) Plant cell, Tissue and organ culture, 8(2) : 153-161．
94． Park YH, Moon EK, Shin YK et al (2000) Antitumor activity of Paecilomyces japonica is mediated by apoptotic cell death. J. Micro Biotec, 10(1) : 16-20
95． Petrini O (1991) Fungal endophtes of tree leaves. In: Andrews J H, Hirano SS eds. Microbial Ecology of Leaves. New York: Springer-Verlag. 179-197．
96． Petrini O, Stone J, Carroll FE (1982) Endophytic fungi in evergreen shrubs in western Oregon: A preliminary study. Can J Bot, 60: 789-796．
97． Prestidge RA, Pottinger RP, Barker GM (1982) An association of Lolium endophyte with ryegrass resistance to Argentine stem weevil. Proc N Z Weed Pest control Conf, 35: 119-122
98． Resnick L (1993) Use of cytochalsins for inhibiting viral replication. International application published under the patent cooperation treaty (PCT), WO 93/11763．
99． Richardson MD, Logendra S (1997) Ergosterol as an indicator of endophyte biomass in grass seeds. J Agric Food chem., 45: 3903-3907．
100． Roberts CA, Barton FE II,Moore KJ (1988) Estimation of Acremonium coenophialum mycelium in infected tall fescue. Agron J, 80: 737-740．
101． Robineau S, Chabre M, Antonny B (2000) Binding site of brefeldin A at the interface between the small G protein ADP-ribosylation factor 1 (ARF1) and the nucleotide-exchange factor Sec7 domain.Proc Natl Acad Sci USA , 97(18) :9913-8．
102． Roth J, Leroith D, Collier ES, Watkinson A, Lesniak MA (1986) The
evolutionary origins of intercellular communication and the Maginot Lines of the mind. Annals of the New York Academy of Sciences, 436: 1-11．
103． Rubtsova SN, Kondratov RV, Kopnin PB, Chumakov PM, Kopnin BP, Vasiliev JM (1998) Disruption of actin microfilaments by cytochalasin D leads to activation of p53． FEBS Lett, 430 (3) : 353-357
104． Sauman I, Berry SJ (1993 ) Cytochalasin-D treatment triggers premature apoptosis of insect ovarian follicle and nurse cells. Int J Dev Biol., 37(3) : 441-450．
105． Semyonov AV, Zazulin SK Stefani DV (1995) Suppression of anaphylactic shock in sensitized guinea pigs by cytochalasin D. Immunol Lett., 47(1-2) :59-62．
106． Service RF (2000) Hazel trees offer new source of cancer drug. Science (Biomedicine), 288(5463) : 27-28．
107． Shin HY, Lee EH, Shin TY, Kim HM (1997) Effect of cytochalsin D on systemic and local anaphylaxis in a murin model. Pharmacol Res, 36(2) : 141-146．
108． Siegel MR (1993) Acremvnium endophytes: our current state of knowledge and future direction for search. Agric Ecosystem Environ, 44: 301-321
109． Siegel MR, Johnson MC, Varney DR Nesmith WC, Buckner RC, Bush LP, Burrus PB, Jones TA, Boling JA (1984) A fungal endophyte in tall fescue: incidence and dissemination. Phytopathology, 74: 932-937．
110． Siegel MR, Latch GCM, Johnson MC (1987) Fungal endophytes of grasses. Ann Rev Phytopathol, 25: 193-315．
111． Singleton VL, Bohonos N and Ullstrup AJ (1958) Decumbin, a new compound from a species of Penicillium. Nature 181:1072-1073．
112． Sings HL, Harris GH (2001) Dombrowski AW.Dihydrocarbazole Alkaloids from Aspergillus tubingensis. J Nat Prod, 64(6) : 836-8．
113． Steller H (1995) Mechanisms and genes of cellular suicide. Science, 267． 1445．
114． Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomycetes andreanae, an endophytic fungus of Pacific Yew. Science, 260(5105) : 214-216．
115． Strobel G, Yang XS, Sears J, Kramer R, Sidhu RS and Hess WM (1996) Taxol from Pestalotiopsis microspora, an endophytic fungus of Taxus wallachiana. Microbiology 142, 435-440．
116． Strobel GA, Torczynskl R, Bollon A (1997) Acremvnium sp.-a leucinostatin A producing endophyte of European yew (Taxus baccata). Plant Science, 128: 97-108．
117． Sugden AM (2000) Ecology & Evolution. Diversity And Infinitum. Science,
289 (5481) : 833-835．
118． Suh YG, Jung JK, Suh BC, Lee YC Kim SA (1998) A formal synthesis of (+)-brefeldin A. Tetrahedron Letters, 39:5377-5380．
119． Suh YG, Seo SY Jung JK Park OH, Jeon RO (2001) A trans-vinylogous ester anion equivalent and its application to the synthesis fo (+)-brefeldin A, Tetrahedron Letters, 42:1691-1694．
120． Suria H, Chau LA, Negrou E, Kelvin DJ, Madrenas J (1999) Cytoskeletal disruption induces T cell apoptosis by a caspase-3 mediated mechanism. Life Science, 65(25) : 2697-2707．
121． Suzuki Y, Tanaka H, Aoki H, Tamura T (1970) Ascotoxin (decumbin), a metabolite of Ascochyta imperfecta Peck, Agric. Biol. Chem. 34395-343413．
122． Tamura G, Ando K, Suzuki S, Takatsuki A and Arima K (1968) Antiviral activity of brefeldin A and verrucarin A. J. Antibiotics, 21: 160-161．
123． Tannenbaum SF (1978) Cytochalasins: Biochemical and biological aspects. North-Holland Publishing Co., Amsterdam, 561．
124． Tsukuda Y, Matsumot M, Minata H and Koyama H (1969) Structure of zygosporin A: X-ray analysis of isozygosporin A p-bromobenzoate, Chem. Comm., 41．
125． Turi TG, Webster P, Rose JK (1994) Brefeldin A sensitivity and resistance in Schizosaccharomyces pombe. Isolation of multiple genes conferring resistance. J Biol Chem, 269(39) : 24229-36．
126． Vandenberg JD, Sandvol LE, Jaronski (2001) Efficacy of fungi for control of Russian wheat aphid (Homoptera: Aphididae) in irrigated wheat. Southwestern Entomologist, 26(1) : 73-85．
127． Vederas JC, Graf W, David L, and Tamm C (1975) Biosynthesis of cytochalasans. Part 4． The mode of incorporation of common naturally-occurring carboxylic acids into cytochalasin D1． Helv Chem Acta., 58(7) :1886-1898．
128． Vurro M, Evidente A, Andolfi A,. Zonno MC, Giordano F, Motta A (1998) Brefeldin A and a,b-dehydrocurvularin, two phytotoxins from Alternaria zinniae, a biocontrol agent of Xanthium occidentale, Plant Science 138, 67-79．
129． Wallen E, Sellers RG, Peehl DM ( 2000 ) Brefeldin A induces p53-independent apoptosis in primary cultures of human prostatic cancer cells. J Urol, 164(3 Pt 1) :836-41．
130． Wang J, li G, Lu H, Zheng Z, Huang Y and Su W (2000) Taxol from Tubercularia sp.strain TF5,n endophytic fungus from Taxus mairei, FEMS Microbiology Letters, 193: 249-253．
131． Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT (1971) Plant
antitumor agents. VI. The isolation and structure of taxol, a novel antilekemic and antitumor agent from Taxus brevifolia. J Am Chem Soc, 93: 2325-2327.
132.Weber HP, Hauser D and Sigg HP (1971) Structure of brefeldin A, Helv. Chem. Acta, 54(8): 2763-2766.
133.White JF, Cole GT (1985) Endophyte-host associations in forage grasses Ⅲ. In vitro inhibition of fungi by Acremvnium coenophialum. Mycologia, 77: 487-489.
134.White JF, Morgan-Jones G, Morrow AC (1993) Taxonomy, life cycle, reproduction and detection of Acremunium endophytes. Agric Ecosystems Environ, 44: 13-37.
135.Wilson AD (1996) Resources and testing of endophyte-infected germplasm in national grass repository collections. In: Redlin SC Carris LM eds. Endophytic fungi in grasses and woody plants: systematics, ecology, and evolution St. Paul, Minnesota: APS Press, 179-195.
136.Yamazaki Y, Tsuruga M, Zhou D, Fujita Y, Shang X, Dang Y, Kawasaki K, Oka S (2000) Cytoskeletal disruption accelerates caspase-3 activation and alters the intracellular membrane reorganization in DNA damage-induced apoptosis. Exp Cell Res, 25; 259(1): 64-78.
137.Yang J, Liu X, Bhalla K, Kim CC, Ibrado AM, Cai J, Teng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science, 275:1129-1132.
138.Yang X, Strobel G, Stierle A, Hess WM, lee J, Clardy J (1994) A fungal endophyte-tree relationship: Phoma sp. in Taxus wallachiana. Plant Science, 102:1-9.
139.Yujiri T, Fanger GR, Garrington TP, Schlesinger TK, Gibson S, Johnson GL (1999) MEK kinase 1 (MEKK1) transduces c-Jun NH2-terminal kinase activation in response to changes in the microtubule cytoskeleton. J Biol Chem Apr 30;274(18):12605-10
140.Zelent A (2001) Hot on the TRAIL of acute promyelocytic leukemia Nat Med. 7(6): 662-4.
141.Zhang JZ, Zhang LH, Wang XH, Qiu D, Sun D, Gu J and Fang Q (1998) Microbial transformation of 10-deacetyl-7-epitaxol and 1β-hydroxybaccatin I by fungi from the inner bark of Taxus yunnanensis, J Nat Prod., 61, 497～500.
142．安建梅，贺运春，白锦荣，张平华(2000)虫生真菌粉质拟青霉对黄刺蛾幼虫的致病性研究，山西农业大学学报，20(2)：105-107
143．柴一秋，张乐人，张辉(2000)几种虫生真菌代谢产物生物活性的初步研究，南京农业大学学报，23(3)：37-40。
144．陈代杰 (1997) 微生物药物的研究开发，中国医药工业杂志(Chinese Journal of Pharmaceuticals)，28(3)。
145．陈锡林(1987)抗癌菌类药常用种类及近代研究简介．浙江中医学院学报，11(1)：62-63。
146．郭波，李海燕，张玲琪(1998)一种产长春碱真菌的分离，云南大学学报(自然科学版)，20(3)：214-215。
147．郭良栋(2001)内生真菌研究进展．菌物系统，20(1)：148-152。
148．韩锐(1997)抗癌药物研究与实验技术，北京医科大学—中国协和医科大学联合出版社，280-350。
149．胡之璧，周秀佳，郭济贤，吴承卫，黄炼栋，吴耀平，章国英(1995) 三尖杉培养细胞中抗癌活性成分的研究．植物学报，37(6)：417-424。
150．黄璐琦，杨滨，王敏等(1999) 当前我国药用植物资源开发利用研究中几个问题的探讨，中国中药杂志，24(2)：70-73。
151．江泽飞，宋三泰，刘晓晴等(1997) 单用国产紫杉醇治疗乳腺癌，中华肿瘤杂志，19(6)：445-447
152．蒋三俊(1990)我国抗癌昆虫药材，中药材，13(11)：11-14。
153．李海燕，王志军，张玲琪，张无敌(1999)一种桃儿七内生真菌的分离初报，云南大学学报(自然科学版)，21(3)：243。
154．李焕娄，蔡年生(1993)，从抗生素到微生物药物，中国抗生素杂志，18(2)：85-89。
155．李全，谢毓元(1996)开发肿瘤化疗药的一些新途径，药学进展，20(3)：129-135。
156．梁宇，高玉葆(2000) 内生真菌对植物生长发育及抗逆性的影响，植物学通报，17(1)：52-59。
157．梁宗琦 (1999)真菌次生代谢产物多样性及其潜在应用价值，生物多样性，(2)：145-150。
158．林风，程元荣(1998)，紫杉醇的生物合成与微生物转化，国外医药抗生素分册，19(1)：22-24。
159．林杰(1987)中国抗癌食用菌名录，微生物学杂志，7(3)：54-56。
160．刘俊达，张靖莲(1999)细胞凋亡研究促进新药开发的展望，中国新药杂志，8 (5)：98-101。
161．吕居娴，李映丽，李小红，焦文旭，张阳，张天宇(1995) 具有抗肿瘤活性的真菌，西北药学杂志，10(10)：226-232。
162．罗明典(1998)微生物制药研究新进展，微生物学通报，25(1)：61-62
163．马天有，董兆麟(1999) 植物分离产紫杉醇的内生真菌的研究，西北大学学报，29(1)：47-49。
164．宁文，曹日强(1993) 真菌诱导物在植物次生代谢中的调节作用，植物生理学通讯，29(5)：321-329。
165．宁文，曹日强(1996)米曲霉中紫草色素诱导物对滇紫草细胞代谢的影响，植物生理学报，22(1)：74-80。
166．宁文，赵群华，夏仲豪(1994) 真菌诱导物在滇紫草细胞培养中对紫草色素形成的影响，植物生理学报，20(4)：325-331。
167．彭玮丹，张杰，王成济(1998)紫杉醇诱导的细胞凋亡信号传导，生命的化学，18(6)：35-37。
168．邱德有，黄美娟，方晓华(1994)一种云南红豆杉内生真菌的分离，真菌学报，13(4)：314-316。
169．邱明华，陆保平，马昕(1997)丽江产三尖杉的生物碱成分，云南植物研究，19(1)：97-99。
170．苏志尧，陈北光(1999)粤北珍稀濒危植物的区系特点和保护对策，林业科学研究，12(1)：23-30。
171．孙震晓，马清温(2000)抗癌药物及其植物组织培养研究进展，微生物学通报，35(8)：11-12。
172．田成国，吴健(1999)红豆杉抗癌有效成分的研究，贵州师范大学学报(自然科学版)，17(4)：19-21。
173．王建锋，吕华鹰，黄耀坚，郑忠辉，苏文金(1999)一株新的紫杉醇产生菌及其抗肿瘤活性，厦门大学学报(自然科学版)，38(4)：485-487。
174．王建锋，吕华鹰，苏文金，植物内生真菌产紫杉醇的研究(2000)微生物学通报，27：58-60。
175．王建锋，苏文金，紫杉醇诱导细胞凋亡机制研究进展(2000)国外医学肿瘤学分册，27：204-207。
176．王伟，贺雄雷，钟英长(1999)南方红豆杉内生菌及紫杉烷类产物的初步鉴定，中山大学学报(自然科学版)，38(3)：116-118。
177．王伟，钟英长(1999)紫杉醇生物合成的研究，植物学通报，16(2)：138-149。
178．王嶽，方金瑞主编(1988)抗生素——抗肿瘤抗生素的筛选，科学出版社，北京，1-522。
179．吴承卫(1993)三尖杉及其生物碱类成分的研究进展，国外医药药学分册，20(6)：321-325
180．新田和男(1989)抗肿瘤药物的筛选，国外医药抗生素分册，10(4)：268-273
181．徐锦堂(1997)中国药用真菌学，北京医科大学、中国协和医科大学联合出版社，北京，1-836。
182．张均田(1998)现代药理实验方法，上册，北京医科大学-中国协和医科大学联合出版社，北京，821-850。
183．赵长琦，许有玲(1997)抗肿瘤植物药及其有效成分——总论，中国中医药出版社，北京，1-24。
184．赵卫红(1998)细胞周期与凋亡．国外医学·放射医学核医学分册 22(2)：88-91。
185．中国药学会抗生素专业委员会(1997)，抗生素科学的发展，中国药学杂志，32(11)：698-700。
2． Ainsworth GC,Sparrow F K and Sussman AS (1973) The fungi, an advanced treatise. Vol. IVA, A taxonomic review with keys: Ascomycetes and fungi imperfecti. Academic press New York and London. 05, 428, 445, 514．
3． Albertsson J, Fex T, Svensson C (1981) X-ray study of Cytochalasin M, a secondary metabolite from the fungus Chalara microspora. Acta Chem.Scand.Ser.A, 35, 707．
4． Aldridge DC and Turner WB (1969) The identity of zygosporin A and cytochalasin D. J. Antibiotic. 170．
5． Alvarez C, Sztul ES (1999) Brefeldin A (BFA) disrupts the organization of the microtubule and the actin cytoskeletons. European Journal of Cell Biology. 78(1) : 1-14．
6． Bacon CW (1993) Antibiotic stress tolerances (moisture, nutrients) and photosynthesis in endophyte infected tall fescue. Agric Ecosystens Environ, 44:123-141．
7． Bacon CW, Lyons PC, Porter JK Robbins JD (1986) Ergot toxicity from endophyte-infected grasses: a review. Agron J, 78: 106-116．
8． Barnett HL and Hunter BB (1977) Illustrated genera of imperfect fungi. (Third edition, Chines version), China scientific press. 144-145．
9． Basualdo JA, Ciarmela ML, Sarmiento PL, Minvielle MC (2000) Biological activity of Paecilomyces genus against Toxocara canis eggs. Parasitology Research, 86(10) : 854-859．
10． Bellag DM, McQuency PA, Zhu J, Hensens O, Konpal L, Liesch J, Geetz M, Larariaes E and Woods CM (1995) Epothilopes, A new class of microtubule-stablizing agents with a taxol-like mechanism of action. Cancer Res. 55, 2325-2333．
11 Beno MA and Christoph GG (1976) X-ray crystal structure of Cytochalasin H, a potent new [11] cytochalasan toxin, Chem. Comm. 344-345． ,
12． Beno MA, Cox RH, Wells JM, Cole RJ, Kirksey JW (1977) Structure of a new [11] cytochalasin, cytochalasin H or Kodo-cytochalasin-1． J.Am.Chem.Soc. 99: 4123-4124．
13． Betina V (1969) Effect of the macrolide antibiotic, cyanein on Hela cell growth and metabolism. Neoplasma, 16:23-32．
14． Betina V (1992) Biological effects of the antibiotic brefeldin A (decumbin,
cyanein, ascotoxin, synergisidin): a etrospec-tive, Folia Microbiol. 37: 3-11．
15． Betina V, Drobnica L, Nemec P and Zemanova M (1964) Study of the antifungal activity of the antibiotic cyanein. J. Antibiotics Ser. A, 17: 353-357．
16． Betina V, Nemec P, Dobias J, and Barath Z (1966) Cyanein, a new antibiotic from Peniciltium cyaneum. Folia Microbiol. (Praha) 7:353-357．
17． Boiler T (1995) Chemoperception of microbial signal in plant cells. Annu Rev Physiol Plant Biol, 46: 189-214．
18． Buchi G, Kitaura Y and Yuan SS (1973) Structure of cytochalasin E, a toxic metabolite of Aspergillus clavatus, J. Am Chem. Soc. 96(16) , 5423-5425．
19． BuLock JD, and Clay PT (1969) ,Fatty acid cyclization in the biosynthesis of brefeldin A; a new route to some fungal metabolites. Chem. Commun, 237-238．
20． Buolamwini JK (1999) Novel anticancer drug discovery, Current Opinion in Chemical Biology, 3: 500-509．
21． Cameron AF, Freer AA, Hesp B, Strawson CJ (1974) Isolation, and crystal and molecular structure of cytochalasin G: an [11] cytochalasan containing an indole group J.Chem.Soc.,Perkin Trans.2, 1741．
22． Carolin DS, Zoe AS, Deborah M, Luo JT (1998) Mitotic phosphorylation of Bcl-2 during Normal cell cycle progression and taxol-induced growth arrest. J. Biol. Chem., 273(46) : 30777-30784．
23． Carroll G (1988) Fungal endophytes in stems and leaves: from latent pathogen to mutualistic symbiont. Ecology, 69: 2-9
24． Carter SB (1967) Effects of cytochalasins on mammalian cells. Nature, 213: 261-264．
25． Chapman JR, Tazaki H, Mallouh C, Konno S (1999) Brefeldin A-induced apoptosis in prostatic cancer DU-145 cells: a possible p53-independent death pathway. BJU Int, 83(6) :703-8．
26． Chardin P. and McCormick F. (1999) , Brefeldin A: The advantage of being uncompetitive. Cell 97:153-155．
27． Cho SW, Kim N, Choi MU, Shin W (2001) Structure of aspergillopepsin I from Aspergillus phoenicis:variations of the SV-S2' subsite in aspartic proteinases. Acta Crystallogr D Biol Crystallogr, 57(Pt 7) :948-56
28． Christen AA, Gibson DM, Bland JB (1991) Production of taxol or taxol-like compounds in cell culture. US patent, 5, 019, 504
29． Clay K (1987) Effects of fungal endophytes on the seed and seedling biology of Lolium perenne and Festuca arundinacea. Cecologia, 73: 358-362．
30． Clay K (1988) Fungal endophytes of grasses: a defensive mutualism. Ecology, 69: 10-16．
31． Clay K (1990) Fungal endophyte of grasses. Annu Rev Ecol Syst, 21: 257-297．
32． Cline SD, Coscia CJ (1988) Stimulation of sanguinary inproduction by combined fungal elicitation and hormonal deprivation in cell suspension cultures of Papaver bracteatum. Plant Physiol, 86: 161-165．
33． Cooper JA (1987) Effects of Cytochalasin and phalloidin on actin. J.cell Biol..105． 1473-1478．
34． Daniel IO, Loy EV (1995) Proteolysis of p6． 9 induced by cytochalasin D in Autographa californica M nuclear ployhedrosis virus-infected cells, virology, 207: 1-11．
35． Daniel MB, McQueney PA, Zhu J, Hensens O, Konpal L, Liesch J, Geetz M, Larariaes, Woods CM (1995) Epothilopes, A new class of microtubule stablizing agents with a taxol-like mechanism of action. Cancer Res., 55: 2325-2333．
36． Demain AL, Hunt NA, Malik V, Kobbe B, Hawkins H, Matsuo K,Wogan GN (1976) Improved procedure for production of cytochalasin E and tremorgenic mycotoxins by Aspergillus clavatus. Appl Environ Microbiol, 31(1) :138-40．
37． Denis JN, Green AE, Gerenard D (1998) A highly efficient, practical approach to natural taxol. J Am Chem Soc, 110 (17) : 5917-5919．
38． Douros J, Suffness M, (1982) . ,9(1) : 17-24．
39． Edward, HK, Kevin J, Volk SE, Hill. (1994) Profiling taxanes in Taxus extracts using LC/MS and LC/MS/MS techniques. J. Natural products. 57, 1391-1403．
40． Eilert U, Kurz WG , Constabel F (1984) Stimulation of sanguinarine accumulation in vapaver somniferum cell cultures by fungal elicitors.J Plant Physiol, 119: 65-76．
41． Entwistle ID, Howard CC, Johnstone RAW (1974) Isolation of brefeldin A from Phyllosticta medicaginis, Phyto-chemistry, 13 173-174．
42． Evidente A, Capasso R, Vurro M, and Bottalica A (1996) Cytochalasin W, a new 24-oxa[14] cytochalasan from Phoma exigua var Nat. Toxins, 4(2) :53-57
43． Evidente A., Lanzetta R., Capasso R., Vurro M.and Bottalico A (1992) Cytochalasin U and V, two new cytochalasans, from Phoma exigua var. heteromorpha, Tetrahedron, 48(30) , 6317-6324．
44． Fex T (1981) Structures of cytochalasin K, L, and M, isolated from Chalara microspora. Tetrahedron Lett., 22(28) ,2703-2706．
45． Fisher P J, Petrini O, Sutton B C (1993) A comparative study of fungal endophytes in leaves, xylem and bark of Eucalyptus nitens in Australia and England. Sydowia, 45: 338-345．
46． Fujii Y, Tani H, Ichinoe M, and Nakajima H (2000) Zygosporin D and two new cytochalasins produced by the fungus Metrarrhizium anisopliae, J. Nat. Prod., 63:132-135．
47． Funk CR, White RH, Breen JP (1993) Importance of Acremvnium endophytes in turf-grass breeding and management. Agric Ecosystem Environ, 44: 215-232．
48． Goddete DW, and Frieden C (1986a) The Kinetics of cytochalasin D binding to monomeric actin. J. Boil. Chem., 261:15970-15973．
49． Goddete DW, and Frieden C (1986b) Actin polymerization, the mechanism of action of cytochalasin D, J. Boil. Chem., 261:15973-15980．
50． Graf W, Robert JL, Vederas JC, Tamm C, Solomon PH, Miura I, Nakanishi K (1974) Biosynthesis of the cytochalsans (Part III. 13C-NMR of cytochalasin B (Phomin) and cytochalsin D incorporation of [1-13C]-and [2-13C]-sodium acetate). Helv. Chem. Ada, 57(6) :1801-1815．
51． Griffin JF, Rampal AL, Jung CY (1980) The structure of cytochalsin A. Am.Cryst.Assoc.Ser.2, 7-13．
52． Guo H, Tittle TV, Allen H, Maziarz RT (1998) Brefeldin A-mediated apoptosis requires the activation of caspases and is inhibited by Bcl-2． Exp Cell Res, 245(1) :57-68．
53． Guptars (1987) Synthesis and biological activities of c4 esters of 4' demethylepipodophyllotoxin. Anticancer Drug Design, 2:13-15．
54． Hacki J, Egger L, Monney L, Conus S, Rosse T, Fellay I, Borner C (2000) Apoptotic crosstalk between the endoplasmic reticulum and mitochondria controlled by Bcl-2． Oncogene, 19(19) :2286-95．
55． Harri E, Loeffier W, Sigg HP, Stahelin H and Tamm C (1963) Ober die isolierung neuer stoffwechselprodukte aus Penicillium brefeldianum DODGE, Helv. Chem. Acta, 46(6) : 1235-1243．
56． Harris JP, Mantle PG (2001) Biosynthesis of by Aspergillus ochraceus. Phytochemistry, 57(2) : 165-9．
57． Hawksworth DL, Sutton BC and Ainsworth GC (1983) Dictionary of the fungi, (Seventh Edition). Common Wealth Mycological Institute, Kew, Surrey. 1-500．
58． Hawksworth, DL (1991) The fungal dimension of biodiversity: magnitude, significance, and conservation. Mycol. Res, 95:641-655．
59． Helms JB and Rothman JE (1992) Inhibition by brefeldin A of a goldi membrane enzyme that catalyses exchange of guanine mucleotide bound to ARF. Nature, 360:352-353．
60． Hezari M and Croteau R (1997) Taxol biosynthesis: an update. Planta Medica 63:291-295．
61． Hinton DM, Bacon CM (1985) The distribution and ultrastructure of endophyte of toxic tall fescue. Can J Bot. 63: 36-42．
62． Huang KC, Hwang YY, Hwu L, Lin A (1997) Characterization of a new ribotoxin gene (c-sar) from Aspergillus clavatus. Toxicon. 35 (3) : 383-92．
63． Hugh R, Pelham B (1991) Multiple targets for brefeldin A. Cell, 67:449-451．
64． Johnson MC, Anderson RL, Krysolo RJ, Siegel MR (1983) Sampling procedure for determining endophyte content in tall fescue seed lots by ELISA. Phytopathology, 73: 1046-1049．
65． Johnson MC, Pirone TP, Siegel MR, Varney DR (1982) Detection of Epichloe typhina in tall fescue by means of enzyme-linked immunosorbent assay. Phytopathology, 72: 647-650．
66． Jordan MA, Toso RJ, Thrower D and Wilson L (1993) Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concertrations. Proc. Natl. Acad. Sci. USA, 90:9552-9556．
67． Kakeya H, Morishita M, Onozawa C, Usami R, Horikoshi K, Kimura K, Yoshihama M and Osada H (1997) RKS-1778, a new mammalian cell-cycle inhibitor and a key intermediate of the [11] cytochalasin group. J. Nat. Prod. 60,669-672．
68． Katagiri K and Matsuura S (1971) Antitumor activity of cytochalasin D. J. Antibiotics, 24(10) : 722-723
69． Kwong YL, Au WY, Chim CS, Pang A, Suen C, Liang R. (2001) Arsenic trioxide-and idarubicin-induced remissions in relapsed acute promyelocytic leukaemia:clinicopathological and molecular features of a pilot study. Am J Hematol., 66(4) :274-9．
70． Li JY, Harper JK, Grant DM, Tombe BO, Bashyal B, Hess WM, Strobel GA (2001 A) Ambuic acid, a highly functionalized cyclohexenone with antifungal activity from Pestalotiopsis spp. and Monochaetia sp.. Phytochemistry, 56: 463-468．
71． Li JY, Sidhu RS, Bollon A,Strobel GA (1998B) Stimulation of taxol production in liquid cultures of Pestalotiopsis microspora. Mycol Res, 102(4) : 461-464．
72． Li JY, Sidhu RS, Ford EJ, Long DM, Hess WM and Strobel GA (1998A) The induction of taxol production in the endophytic fungus-Periconia sp. from Torreya grandifolia. J. Industrial Microbiology & biotechnology, 20(5) : 259-264．
73． Li JY, Strobel GA (2001B) Jesterone and hydroxy-jesterone antioomycete cyclohexenone epoxides from the endophytic fungus Pestalotiopsis jesteri. Phytochemistry, 57: 261-265．
74． Lin DC, Tobin KD, Grumet M and Lin S (1980) Cytochalasins inhibit nuclei-induced actin polymerization by blocking filament elongation. J. Cell Biol., 84:455-460．
75． Lopez-Diaz TM, Flannigan B. ( 1997 ) Production of patulin and cytochalasin E by Aspergillus clavatus during malting of barley and wheat. Int J Food Microbiol, 35(2) :129-36．
76． Lu H, Zou WX, Meng JC, Hu J, Tan RX (2000) New bioactive metabolites produced by Colletotrichum sp., an endophytic fungus in Artemisia annua. Plant Science, 151(1) : 67-73．
77． Mabuni CT, Garlaschelli L, Ellison RA, Hutchinson CR (1977) Biosynthetic origin of the oxygen atoms in the C15 macrolide antibiotic brefeldin A J Am Chem Soc, 99(23) : 7718-20．
78． Maccotta A, Vaiensin G, Gaggelli N, Gaggelli E (1993) The conformation of cytochalasin D in DMSO solution frm 1H and 13C NMR relaxation rates. J. Chem. Soc. Perkin Trans.2, 729-732．
79． Manti L, Bowen ID, Mason MD, Court JB (2000) Apoptosis is a mode of cell death in the polykaryon-forming unit assay. Cell Biol Int 24(7) :415-25
80． Marks S, Clay K (1996) Physiological responses of Festuca arundinacea to fungal endophyte infection. New Phytol, 133: 727-733．
81． Mclaughlin G, Sim GA, Kiechel JR and Tamm C (1970) Chem. Comm., 1398-1399．
82． McMillan JA, Chiang CC, Greensley MK, Paul IC, Patwardhan SA, Dev S, Beno MA, Christoph GG (1977) X-ray crystal and molecular structure of kodo-cytochalasin-1, Chem.Comm., 105-106．
83． Miata H and Matsumoto M (1970) Studies of the metabolites of Zygosporium masonu, Part I.Structure of zygosporin A., J. Chem. Soc.(C), 38-47．
84． Munshi NC. (2001) Arsenic trioxide: an emerging therapy for multiple myeloma. Oncologist.Suppl, 2:17-21．
85． Murgo AJ (2001) Clinical trials of arsenic trioxide in hematologic and solid tumors: overview of the National Cancer Institute Cooperative Research and Development Studies. Oncologist. Suppl 2:22-8．
86． Nagasawa H, Nagura R, Mohamad SB, Uto Y, Zhu JW, Tsukuda T, Hashimoto T, Asakawa Y. Hori H (2000) , Apoptosis induction oin HCT116 cells by cytochalasin isolated from the fungus Daldinia vernicosa, Phytomedicine, 6(6) : 403-409．
87． Nicolaou KC, Yang Z, Liu JJ, Ueno H, Nantermet PG, Guy RK, Claiborne CF, Renaud J, Couladouros EA, Paulvannan K, Sorense EJ. (1994) Total xynthesis of taxol. Nature. 367: 630-634．
88． Nicole B, Nicole M (1999) Cell biology of plant immunization against
microbial infection: The potential of induced resistance in controlling plant diseases. Plant Physiol Biochem, 37(10) : 703-719
89． Nilanonta C,Isaka M, Kittakoop P, Palittapongarnpim P, Kamchonwongpaisan S, Pittayakhajonwut D, Tanticharoen M, Thebtaranonth Y (2000) Antimycobacterial and antiplasmodial cyclodepsipeptides from the insect pathogenic fungus Paecilomyces tenuipes BCC1614． Planta Medica, 66(8) : 756-758．
90． Nisbet LJ, Fox FM (1991) The importance of microbiodiversity to biotechnology. Hawksworth D L (ed) The Biodiversity of Microorganisms and Invertebrates: Its Role in Sustainable Agriculture, 229-244．
91． Noh MJ, Yang JG, Kim KS, Yoon YM, Kang KA, Han HY, Shim SB, Park HJ (1999) Isolation of a novel microorganism, Pestalotia heterocornis, producing paclitaxel. Biotechnology And Bioengineering, 64(5) : 620-623．
92． Ohmori H, Toyama Su and Toyama Sa (1992) Direct proof that the primary site of action of cytochalasin on cell motility processes is actin, J. cell Biol. 116: 933-941．
93． Otmar S, Jochen B (1987) Plant cell, Tissue and organ culture, 8(2) : 153-161．
94． Park YH, Moon EK, Shin YK et al (2000) Antitumor activity of Paecilomyces japonica is mediated by apoptotic cell death. J. Micro Biotec, 10(1) : 16-20
95． Petrini O (1991) Fungal endophtes of tree leaves. In: Andrews J H, Hirano SS eds. Microbial Ecology of Leaves. New York: Springer-Verlag. 179-197．
96． Petrini O, Stone J, Carroll FE (1982) Endophytic fungi in evergreen shrubs in western Oregon: A preliminary study. Can J Bot, 60: 789-796．
97． Prestidge RA, Pottinger RP, Barker GM (1982) An association of Lolium endophyte with ryegrass resistance to Argentine stem weevil. Proc N Z Weed Pest control Conf, 35: 119-122
98． Resnick L (1993) Use of cytochalsins for inhibiting viral replication. International application published under the patent cooperation treaty (PCT), WO 93/11763．
99． Richardson MD, Logendra S (1997) Ergosterol as an indicator of endophyte biomass in grass seeds. J Agric Food chem., 45: 3903-3907．
100． Roberts CA, Barton FE II,Moore KJ (1988) Estimation of Acremonium coenophialum mycelium in infected tall fescue. Agron J, 80: 737-740．
101． Robineau S, Chabre M, Antonny B (2000) Binding site of brefeldin A at the interface between the small G protein ADP-ribosylation factor 1 (ARF1) and the nucleotide-exchange factor Sec7 domain.Proc Natl Acad Sci USA , 97(18) :9913-8．
102． Roth J, Leroith D, Collier ES, Watkinson A, Lesniak MA (1986) The
evolutionary origins of intercellular communication and the Maginot Lines of the mind. Annals of the New York Academy of Sciences, 436: 1-11．
103． Rubtsova SN, Kondratov RV, Kopnin PB, Chumakov PM, Kopnin BP, Vasiliev JM (1998) Disruption of actin microfilaments by cytochalasin D leads to activation of p53． FEBS Lett, 430 (3) : 353-357
104． Sauman I, Berry SJ (1993 ) Cytochalasin-D treatment triggers premature apoptosis of insect ovarian follicle and nurse cells. Int J Dev Biol., 37(3) : 441-450．
105． Semyonov AV, Zazulin SK Stefani DV (1995) Suppression of anaphylactic shock in sensitized guinea pigs by cytochalasin D. Immunol Lett., 47(1-2) :59-62．
106． Service RF (2000) Hazel trees offer new source of cancer drug. Science (Biomedicine), 288(5463) : 27-28．
107． Shin HY, Lee EH, Shin TY, Kim HM (1997) Effect of cytochalsin D on systemic and local anaphylaxis in a murin model. Pharmacol Res, 36(2) : 141-146．
108． Siegel MR (1993) Acremvnium endophytes: our current state of knowledge and future direction for search. Agric Ecosystem Environ, 44: 301-321
109． Siegel MR, Johnson MC, Varney DR Nesmith WC, Buckner RC, Bush LP, Burrus PB, Jones TA, Boling JA (1984) A fungal endophyte in tall fescue: incidence and dissemination. Phytopathology, 74: 932-937．
110． Siegel MR, Latch GCM, Johnson MC (1987) Fungal endophytes of grasses. Ann Rev Phytopathol, 25: 193-315．
111． Singleton VL, Bohonos N and Ullstrup AJ (1958) Decumbin, a new compound from a species of Penicillium. Nature 181:1072-1073．
112． Sings HL, Harris GH (2001) Dombrowski AW.Dihydrocarbazole Alkaloids from Aspergillus tubingensis. J Nat Prod, 64(6) : 836-8．
113． Steller H (1995) Mechanisms and genes of cellular suicide. Science, 267． 1445．
114． Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomycetes andreanae, an endophytic fungus of Pacific Yew. Science, 260(5105) : 214-216．
115． Strobel G, Yang XS, Sears J, Kramer R, Sidhu RS and Hess WM (1996) Taxol from Pestalotiopsis microspora, an endophytic fungus of Taxus wallachiana. Microbiology 142, 435-440．
116． Strobel GA, Torczynskl R, Bollon A (1997) Acremvnium sp.-a leucinostatin A producing endophyte of European yew (Taxus baccata). Plant Science, 128: 97-108．
117． Sugden AM (2000) Ecology & Evolution. Diversity And Infinitum. Science,
289 (5481) : 833-835．
118． Suh YG, Jung JK, Suh BC, Lee YC Kim SA (1998) A formal synthesis of (+)-brefeldin A. Tetrahedron Letters, 39:5377-5380．
119． Suh YG, Seo SY Jung JK Park OH, Jeon RO (2001) A trans-vinylogous ester anion equivalent and its application to the synthesis fo (+)-brefeldin A, Tetrahedron Letters, 42:1691-1694．
120． Suria H, Chau LA, Negrou E, Kelvin DJ, Madrenas J (1999) Cytoskeletal disruption induces T cell apoptosis by a caspase-3 mediated mechanism. Life Science, 65(25) : 2697-2707．
121． Suzuki Y, Tanaka H, Aoki H, Tamura T (1970) Ascotoxin (decumbin), a metabolite of Ascochyta imperfecta Peck, Agric. Biol. Chem. 34395-343413．
122． Tamura G, Ando K, Suzuki S, Takatsuki A and Arima K (1968) Antiviral activity of brefeldin A and verrucarin A. J. Antibiotics, 21: 160-161．
123． Tannenbaum SF (1978) Cytochalasins: Biochemical and biological aspects. North-Holland Publishing Co., Amsterdam, 561．
124． Tsukuda Y, Matsumot M, Minata H and Koyama H (1969) Structure of zygosporin A: X-ray analysis of isozygosporin A p-bromobenzoate, Chem. Comm., 41．
125． Turi TG, Webster P, Rose JK (1994) Brefeldin A sensitivity and resistance in Schizosaccharomyces pombe. Isolation of multiple genes conferring resistance. J Biol Chem, 269(39) : 24229-36．
126． Vandenberg JD, Sandvol LE, Jaronski (2001) Efficacy of fungi for control of Russian wheat aphid (Homoptera: Aphididae) in irrigated wheat. Southwestern Entomologist, 26(1) : 73-85．
127． Vederas JC, Graf W, David L, and Tamm C (1975) Biosynthesis of cytochalasans. Part 4． The mode of incorporation of common naturally-occurring carboxylic acids into cytochalasin D1． Helv Chem Acta., 58(7) :1886-1898．
128． Vurro M, Evidente A, Andolfi A,. Zonno MC, Giordano F, Motta A (1998) Brefeldin A and a,b-dehydrocurvularin, two phytotoxins from Alternaria zinniae, a biocontrol agent of Xanthium occidentale, Plant Science 138, 67-79．
129． Wallen E, Sellers RG, Peehl DM ( 2000 ) Brefeldin A induces p53-independent apoptosis in primary cultures of human prostatic cancer cells. J Urol, 164(3 Pt 1) :836-41．
130． Wang J, li G, Lu H, Zheng Z, Huang Y and Su W (2000) Taxol from Tubercularia sp.strain TF5,n endophytic fungus from Taxus mairei, FEMS Microbiology Letters, 193: 249-253．
131． Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT (1971) Plant
antitumor agents. VI. The isolation and structure of taxol, a novel antilekemic and antitumor agent from Taxus brevifolia. J Am Chem Soc, 93: 2325-2327.
132.Weber HP, Hauser D and Sigg HP (1971) Structure of brefeldin A, Helv. Chem. Acta, 54(8): 2763-2766.
133.White JF, Cole GT (1985) Endophyte-host associations in forage grasses Ⅲ. In vitro inhibition of fungi by Acremvnium coenophialum. Mycologia, 77: 487-489.
134.White JF, Morgan-Jones G, Morrow AC (1993) Taxonomy, life cycle, reproduction and detection of Acremunium endophytes. Agric Ecosystems Environ, 44: 13-37.
135.Wilson AD (1996) Resources and testing of endophyte-infected germplasm in national grass repository collections. In: Redlin SC Carris LM eds. Endophytic fungi in grasses and woody plants: systematics, ecology, and evolution St. Paul, Minnesota: APS Press, 179-195.
136.Yamazaki Y, Tsuruga M, Zhou D, Fujita Y, Shang X, Dang Y, Kawasaki K, Oka S (2000) Cytoskeletal disruption accelerates caspase-3 activation and alters the intracellular membrane reorganization in DNA damage-induced apoptosis. Exp Cell Res, 25; 259(1): 64-78.
137.Yang J, Liu X, Bhalla K, Kim CC, Ibrado AM, Cai J, Teng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science, 275:1129-1132.
138.Yang X, Strobel G, Stierle A, Hess WM, lee J, Clardy J (1994) A fungal endophyte-tree relationship: Phoma sp. in Taxus wallachiana. Plant Science, 102:1-9.
139.Yujiri T, Fanger GR, Garrington TP, Schlesinger TK, Gibson S, Johnson GL (1999) MEK kinase 1 (MEKK1) transduces c-Jun NH2-terminal kinase activation in response to changes in the microtubule cytoskeleton. J Biol Chem Apr 30;274(18):12605-10
140.Zelent A (2001) Hot on the TRAIL of acute promyelocytic leukemia Nat Med. 7(6): 662-4.
141.Zhang JZ, Zhang LH, Wang XH, Qiu D, Sun D, Gu J and Fang Q (1998) Microbial transformation of 10-deacetyl-7-epitaxol and 1β-hydroxybaccatin I by fungi from the inner bark of Taxus yunnanensis, J Nat Prod., 61, 497～500.
142．安建梅，贺运春，白锦荣，张平华(2000)虫生真菌粉质拟青霉对黄刺蛾幼虫的致病性研究，山西农业大学学报，20(2)：105-107
143．柴一秋，张乐人，张辉(2000)几种虫生真菌代谢产物生物活性的初步研究，南京农业大学学报，23(3)：37-40。
144．陈代杰 (1997) 微生物药物的研究开发，中国医药工业杂志(Chinese Journal of Pharmaceuticals)，28(3)。
145．陈锡林(1987)抗癌菌类药常用种类及近代研究简介．浙江中医学院学报，11(1)：62-63。
146．郭波，李海燕，张玲琪(1998)一种产长春碱真菌的分离，云南大学学报(自然科学版)，20(3)：214-215。
147．郭良栋(2001)内生真菌研究进展．菌物系统，20(1)：148-152。
148．韩锐(1997)抗癌药物研究与实验技术，北京医科大学—中国协和医科大学联合出版社，280-350。
149．胡之璧，周秀佳，郭济贤，吴承卫，黄炼栋，吴耀平，章国英(1995) 三尖杉培养细胞中抗癌活性成分的研究．植物学报，37(6)：417-424。
150．黄璐琦，杨滨，王敏等(1999) 当前我国药用植物资源开发利用研究中几个问题的探讨，中国中药杂志，24(2)：70-73。
151．江泽飞，宋三泰，刘晓晴等(1997) 单用国产紫杉醇治疗乳腺癌，中华肿瘤杂志，19(6)：445-447
152．蒋三俊(1990)我国抗癌昆虫药材，中药材，13(11)：11-14。
153．李海燕，王志军，张玲琪，张无敌(1999)一种桃儿七内生真菌的分离初报，云南大学学报(自然科学版)，21(3)：243。
154．李焕娄，蔡年生(1993)，从抗生素到微生物药物，中国抗生素杂志，18(2)：85-89。
155．李全，谢毓元(1996)开发肿瘤化疗药的一些新途径，药学进展，20(3)：129-135。
156．梁宇，高玉葆(2000) 内生真菌对植物生长发育及抗逆性的影响，植物学通报，17(1)：52-59。
157．梁宗琦 (1999)真菌次生代谢产物多样性及其潜在应用价值，生物多样性，(2)：145-150。
158．林风，程元荣(1998)，紫杉醇的生物合成与微生物转化，国外医药抗生素分册，19(1)：22-24。
159．林杰(1987)中国抗癌食用菌名录，微生物学杂志，7(3)：54-56。
160．刘俊达，张靖莲(1999)细胞凋亡研究促进新药开发的展望，中国新药杂志，8 (5)：98-101。
161．吕居娴，李映丽，李小红，焦文旭，张阳，张天宇(1995) 具有抗肿瘤活性的真菌，西北药学杂志，10(10)：226-232。
162．罗明典(1998)微生物制药研究新进展，微生物学通报，25(1)：61-62
163．马天有，董兆麟(1999) 植物分离产紫杉醇的内生真菌的研究，西北大学学报，29(1)：47-49。
164．宁文，曹日强(1993) 真菌诱导物在植物次生代谢中的调节作用，植物生理学通讯，29(5)：321-329。
165．宁文，曹日强(1996)米曲霉中紫草色素诱导物对滇紫草细胞代谢的影响，植物生理学报，22(1)：74-80。
166．宁文，赵群华，夏仲豪(1994) 真菌诱导物在滇紫草细胞培养中对紫草色素形成的影响，植物生理学报，20(4)：325-331。
167．彭玮丹，张杰，王成济(1998)紫杉醇诱导的细胞凋亡信号传导，生命的化学，18(6)：35-37。
168．邱德有，黄美娟，方晓华(1994)一种云南红豆杉内生真菌的分离，真菌学报，13(4)：314-316。
169．邱明华，陆保平，马昕(1997)丽江产三尖杉的生物碱成分，云南植物研究，19(1)：97-99。
170．苏志尧，陈北光(1999)粤北珍稀濒危植物的区系特点和保护对策，林业科学研究，12(1)：23-30。
171．孙震晓，马清温(2000)抗癌药物及其植物组织培养研究进展，微生物学通报，35(8)：11-12。
172．田成国，吴健(1999)红豆杉抗癌有效成分的研究，贵州师范大学学报(自然科学版)，17(4)：19-21。
173．王建锋，吕华鹰，黄耀坚，郑忠辉，苏文金(1999)一株新的紫杉醇产生菌及其抗肿瘤活性，厦门大学学报(自然科学版)，38(4)：485-487。
174．王建锋，吕华鹰，苏文金，植物内生真菌产紫杉醇的研究(2000)微生物学通报，27：58-60。
175．王建锋，苏文金，紫杉醇诱导细胞凋亡机制研究进展(2000)国外医学肿瘤学分册，27：204-207。
176．王伟，贺雄雷，钟英长(1999)南方红豆杉内生菌及紫杉烷类产物的初步鉴定，中山大学学报(自然科学版)，38(3)：116-118。
177．王伟，钟英长(1999)紫杉醇生物合成的研究，植物学通报，16(2)：138-149。
178．王嶽，方金瑞主编(1988)抗生素——抗肿瘤抗生素的筛选，科学出版社，北京，1-522。
179．吴承卫(1993)三尖杉及其生物碱类成分的研究进展，国外医药药学分册，20(6)：321-325
180．新田和男(1989)抗肿瘤药物的筛选，国外医药抗生素分册，10(4)：268-273
181．徐锦堂(1997)中国药用真菌学，北京医科大学、中国协和医科大学联合出版社，北京，1-836。
182．张均田(1998)现代药理实验方法，上册，北京医科大学-中国协和医科大学联合出版社，北京，821-850。
183．赵长琦，许有玲(1997)抗肿瘤植物药及其有效成分——总论，中国中医药出版社，北京，1-24。
184．赵卫红(1998)细胞周期与凋亡．国外医学·放射医学核医学分册 22(2)：88-91。
185．中国药学会抗生素专业委员会(1997)，抗生素科学的发展，中国药学杂志，32(11)：698-700。