Discovery of potential anticancer agents from aquatic cyanobacteria, filamentous fungi, and tropical plants

Bioactive Compounds from Natural Sources: Natural Products as Lead Compounds in Drug Discovery, Second Edition

Volumn , Issue , 2011, Pages 37-64

  Orjala, Jimmy ^a   Oberlies, Nicholas H ^b   Pearce, Cedric J ^c   Swanson, Steven M ^a   Kinghorn, A Douglas ^d  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b UNIVERSITY OF NORTH CAROLINA AT GREENSBORO   (United States)

^c Mycosynthetix Inc   (United States)

^d OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84856412719     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (149)

1. Adams, J. 2003. Potential for proteasome inhibition in the treatment of cancer. Drug Discov. Today 8:307-315.
2. Aggarwal, B. B., H. Ichikawa, P. Garodia, P. Weerasinghe, G. Sethi, I. D. Bhatt, M. K. Pandey, S. Shishodia, and M. G. Nair. 2006. From traditional medicine to modern medicine: Identification of therapeutic targets for suppression of inflammation and cancer. Expert Opin. Ther. Targets 10:87-118.
3. Alley, M. C., M. G. Hollingshead, D. J. Dykes, and W. R. Waud. 2004. Human tumor xeno¬graft models in NCI drug development. In Anticancer Drug Development Guide, eds. B. A. Teicher and P. A. Andrews, pp. 125-152. Totowa, NJ: Humana Press.
4. Alley, M. C., C. M. Pacula-Cox, M. L. Hursey, L. R. Rubinstein, and M. R. Boyd. 1991. Morphometric and colorimetric analyses of human tumor cell line growth and drug sen¬sitivity in soft agar culture. Cancer Res. 51:1247-1256.
5. Anadu, N. O., V. J. Davisson, and M. Cushman. 2006. Synthesis and anticancer activity of brefeldin A ester derivatives. J. Med. Chem. 49:3897-3905.
6. Andersen, R. A. and M. Kawachi. 2005. Traditional microalgae isolation techniques. In Algal Culturing Techniques, ed. R. A. Andersen, pp. 83-100. San Diego, CA: Academic Press.
7. Arguello, F., M. Alexander, J. A. Sterry, G. Tudor, E. M. Smith, N. T. Kalavar, J. F. Greene, W. Koss, Jr., C. D. Morgan, S. F. Stinson, T. J. Siford, W. G. Alvord, R. L. Klabansky, and E. A. Sausville. 1998. Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity in vivo against human leukemia and lymphoma xenografts. Blood 91:2482-2490.
8. Baaske, D. M. and P. Heinstein. 1977. Cytotoxicity and cell cycle specificity of homohar¬ringtonine. Antimicrob. Agents Chemother. 12:298-300.
9. Bagli, J. F., D. Kluepfel, and M. St. Jacque. 1973. Elucidation of structure and stereochemistry of myriocin. A novel antifungal antibiotic. J. Org. Chem. 38:1253-1260.
10. Bailly, C. 2009. Ready for a comeback of natural products in oncology. Biochem. Pharmacol. 77:1447-1457.
11. Balunas, M. J., W. P. Jones, Y.-W. Chin, Q. Mi, N. R. Farnsworth, D. D. Soejarto, G. A. Cordell, S. M. Swanson, J. M. Pezzuto, H.-B. Chai, and A. D. Kinghorn. 2006. Relationships between inhibitory activity against a cancer cell line panel, profiles of plants collected, and compound classes isolated in an anticancer drug discovery project. Chem. Biodivers. 3:897-915.
12. Bellmunt, J., C. Théodore, T. Demkov, B. Komyakov, L. Sengelov, G. Daugaard, A. Caty, J. Carles, A. Jagiello-Gruszfeld, O. Karyakin, F. M. Delgado, P. Hurteloup, N. Morsli, Y. Salhi, S. Culine, and H. von der Maase. 2009. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J. Clin. Oncol. 27:4454-4461.
13. Berdy, J. 2005. Bioactive microbial metabolites. A personal view. J. Antibiot. (Tokyo) 58:1-26.
14. Bloom, J., V. Amador, F. Bartolini, G. DeMartino, and M. Pagano. 2003. Proteasome-mediated degradation of p21 via N-terminal ubiquitinylation. Cell 115:71-82.
15. Brown, A. G., T. C. Smale, T. J. King, R. Hasenkamp, and R. H. Thompson. 1976. Crystal and molecular structure of compactin, a new antifungal metabolite from Penicillium brevi¬compactum. J. Chem. Soc., Perkin Trans. 1:1165-1170.
16. Buss, A. D., B. Cox, and R. D. Waigh. 2003. Natural products as leads for new pharmaceu¬ticals. In Burger’s Medicinal Chemistry and Drug Discovery, 6th edn., Vol. 1, Drug discovery, ed. D. J. Abraham, pp. 847-900. Hoboken, NJ: Wiley-Interscience.
17. Butler, M. S. 2008. Natural products to drugs: Natural product-derived compounds in clinical trials. Nat. Prod. Rep. 25:475-516.
18. Butler, M. S. 2010. A snapshot of natural product-derived compounds in late stage clinical development at the end of 2008. In Natural Product Chemistry for Drug Discovery, eds. A. D. Buss and M. S. Butler, pp. 321-354. Cambridge, U.K.: Royal Society of Chemistry.
19. Byrd, J. C., T. S. Lin, J. T. Dalton, D. Wu, M. A. Phelps, B. Fischer, M. Moran, K. A. Blum, B. Rovin, M. Brooker-McEldowney, S. Broering, L. J. Schaaf, A. J. Johnson, D. M. Lucas, N. A. Heerema, G. Lozanski, D. C. Young, J.-R. Suarez, A. D. Colevas, and M. R. Grever. 2007. Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood 109:399-404.
20. Carlson, R. O. 2008. New tubulin targeting agents currently in clinical development. Expert Opin. Invest. Drugs 17:707-722.
21. Carmichael, W. W. 1992. Cyanobacteria secondary metabolites-The cyanotoxins. J. Appl. Bacteriol. 72:445-459.
22. Chlipala, G., S. Mo, E. J. Carcache de Blanco, A. Ito, S. Bazarek, and J. Orjala. 2009. Investigation of antimicrobial and protease-inhibitory activity from cultured cyanobac¬teria. Pharm. Biol. 47:53-60.
23. Choueiri, T. K., R. Wesolowski, and T. M. Mekjail. 2006. Phenoxodiol: Isoflavone analog with antineoplastic activity. Curr. Oncol. Rep. 8:104-107.
24. Christian, B. A., M. R. Grever, J. C. Byrd, and T. S. Lin. 2009. Flavopiridol in chronic lympho¬cytic leukemia: A concise review. Clin. Lymph. Myel. 9(Suppl. 3):S179-S185.
25. Chua, C. W., Y. T. Chiu, H. F. Yuen, K. W. Chan, K. Man, X. Wang, M. T. Ling, and Y. C. Wong. 2009. Suppression of androgen-independent prostate cancer cell aggressiveness by FTY720: Validating Runx2 as a potential antimetastatic drug screening platform. Clin. Cancer Res. 15:4322-4335.
26. Chua, C. W., D. T. Lee, M. T. Ling, C. Zhou, K. Man, J. Ho, F. L. Chan, X. Wang, and Y. C. Wong. 2005. FTY720, a fungus metabolite, inhibits in vivo growth of androgen-inde¬pendent prostate cancer. Int. J. Cancer 117:1039-1048.
27. Ciechanover, A. 1994. The ubiquitin-proteasome proteolytic pathway. Cell 79:13-21.
28. Cordell, G. A. 2010. The convention on biological diversity and its impact on natural product research. In Natural Product Chemistry for Drug Discovery, eds. A. D. Buss and M. S. Butler, pp. 81-139. Cambridge, U.K.: Royal Society of Chemistry.
29. Cragg, G. M., P. M. Grothaus, and D. J. Newman. 2009. Impact on natural products on devel¬oping new anti-cancer agents. Chem. Rev. 109:3012-3043.
30. Cragg, G. M., D. G. I. Kingston, and D. J. Newman. 2005. Anticancer Agents from Natural Products. Boca Raton, FL: CRC/Taylor & Francis.
31. Cragg, G. M. and D. J. Newman. 2005. Plants as a source of anticancer agents. J. Ethnopharmacol. 100:72-79.
32. Crawford, J. M., T. P. Korman, J. W. Labonte, A. L. Vagstad, E. A. Hill, O. Kamari-Bidkorpeh, S. C. Tsai, and C. A. Townsend. 2009. Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization. Nature 461:1139-1143.
33. Crawford, J. M., P. M. Thomas, J. R. Scheerer, A. L. Vagstad, N. L. Kelleher, and C. A. Townsend. 2008. Deconstruction of iterative multidomain polyketide synthase function. Science 320:243-246.
34. De Arruda, M., C. A. Cocchiaro, C. M. Nelson, C. M. Grinnell, B. Janssen, A. Haupt, and T. Barlozzari. 1995. LU103793 (NSC D-669356): A synthetic peptide that interacts with microtubules and inhibits mitosis. Cancer Res. 55:3085-3092.
35. De Marais, D. J. 2000. Evolution. When did photosynthesis emerge on earth? Science 289:1703-1705.
36. Douglas, S. E. 1994. Chloroplast origins and evolution. In The Molecular Biology of Cyanobacteria, ed. D. A. Bryant, pp. 91-118. Dordrecht, the Netherlands: Kluwer Academic Publishers.
37. Dreyfus, M., E. Harri, H. Hofmann, W. Pache, and H. Tscherter. 1976. Cyclosporine A and C new metabolites from Trichoderma polysporum. Eur. J. Appl. Microbiol. 3:125-133.
38. El-Deiry, W. S., T. Tokino, V. E. Velculescu, D. B. Levy, R. Parsons, J. M. Trent, D. Lin, W. E. Mercer, K. W. Kinzler, and B. Vogelstein. 1993. Waf1, a potential mediator of p53 tumor suppression. Cell 75:817-825.
39. Erlichman, C. 2009. Tanespimycin: The opportunities and challenges of targeting heat shock protein 90. Expert Opin. Investig. Drugs 18:861-868.
40. Falch, B. S., G. M. Koenig, A. D. Wright, O. Sticher, C. K. Angerhofer, J. M. Pezzuto, and H. Bachmann. 1995. Biological activities of cyanobacteria: Evaluation of extracts and pure compounds. Planta Med. 61:321-328.
41. Fleming, A. 1946. Penicillin, Its Practical Application, 380pp. London, U.K.: Butterworth & Co., Ltd.
42. Gao, J., Y. X. Huang, and Y. K. Wu. 2008. Enantioselective total synthesis of 13-O-brefeldin A. Tetrahedron 64:11105-11109.
43. Gerwick, W., L. T. Tan, and N. Sitachitta. 2001. Nitrogen-containing metabolites from marine cyanobacteria. In The Alkaloids, Vol. 57, ed. G. A. Cordell, pp. 75-184. San Diego, CA: Academic Press.
44. Glaser, K. B. 2007. HDAC inhibitors: Clinical update and mechanism-based potential. Biochem. Pharmacol. 74:659-671.
45. Golakoti, T., I. Ohtani, D. J. Patterson, R. E. Moore, T. H. Corbett, F. A. Valerlote, and L. Demchik. 1994. Total structures of cryptophycins, potent antitumor depsi¬peptides from the blue-green alga Nostoc sp. strain GSV 224. J. Am. Chem. Soc. 116:4729-4737.
46. Harmon, A. D., U. Weiss, and J. V. Silverton. 1979. The structure of rohitukine, the main alkaloid of Amoora rohituka (syn. Aphanamixis polystachya) (Meliaceae). Tetrahedron Lett. 721-724.
47. Harvey, A. L. 2008. Natural products in drug discovery. Drug Discov. Today 13:894-901.
48. Haupt, Y., R. Maya, A. Kazaz, and M. Oren. 1997. MDM2 promotes the rapid degradation of p53. Nature 387:296-299.
49. Hawksworth, D. L. and A. Y. Rossman. 1997. Where are all the undescribed fungi? Phytopathology 87:888-891.
50. Herper, M. 2008. Pfizer wins longer life for Lipitor. Forbes.com. June 18, 2008.
51. Hollingshead, M. G., M. C. Alley, R. F. Camalier, B. J. Abbott, J. G. Mayo, L. Malspeis, and M. R. Grever. 1995. In vivo cultivation of tumor cells in hollow fibers. Life Sci. 57:131-141.
52. Hollingshead, M. G., J. Plowman, M. C. Alley, J. G. Mayo, and E. A. Sausville. 1999. The hol¬low fiber assay. In Relevance of Tumor Models for Anticancer Drug Development, eds. H. H. Fiebig and A. M. Burger, pp. 109-120. Basel, Switzerland: Karger AG.
53. Honda, R., H. Tanaka, and H. Yasuda. 1997. Oncoprotein mdm2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420:25-27.
54. Horti, J., E. Juhasz, Z. Monostori, K. Maeda, S. Eckhardt, and I. Bodrogi. 2008. Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative, for the treatment of patients with non-small cell lung cancer. Cancer Chemother. Pharmacol. 62:173-180.
55. Hutchinson, C. R., I. Kurobane, C. T. Mabuni, R. W. Kumola, A. G. McInnes, and J. A. Walter. 1981. Biosynthesis of macrolide antibiotics. 3. Regiochemistry of isotopic hydrogen labeling of brefeldin A by acetate. J. Am. Chem. Soc. 103:2474-2477.
56. Hutchinson, C. R., S. W. Li, A. G. McInnes, and J. A. Walter. 1983. Comparative biochemistry of fatty-acid and macrolide antibiotic (brefeldin-A)-Formation in Penicillium brefeld¬ianum. Tetrahedron 39:3507-3513.
57. Itokawa, H., S. L. Morris-Natschke, T. Akiyama, and K.-H. Lee. 2008. Plant-derived natural product research aimed at new drug discovery. J. Nat. Med. 62:263-280.
58. Itokawa, H., X. Wang, and K.-H. Lee. 2005. Homoharringtonine and related compounds. In Anticancer Agents from Natural Products, eds. G. M. Cragg, D. G. I. Kingston, and D. J. Newman, pp. 47-70. Boca Raton, FL: CRC/Taylor & Francis.
59. Jemal, S., R. Siegel, E. Ward, Y. Hao, J. Xu, and M. J. Thun. 2009. Cancer statistics, 2009. CA Cancer J. Clin. 59:225-249.
60. Jones, W. P., Y.-W. Chin, and A. D. Kinghorn. 2006. The role of pharmacognosy in modern medicine and pharmacy. Curr. Drug Targets 7:247-264.
61. Kantarjian, H. M., M. Talpaz, V. Santini, A. Mungo, B. Cheson, and S. M. O’Brien. 2001. Homoharringtonine: History, current research, and future direction. Cancer 92:1591-1605.
62. Keller, N. P., G. Turner, and J. W. Bennett. 2005. Fungal secondary metabolism-From bio¬chemistry to genomics. Nat. Rev. Microbiol. 3:937-947.
63. Kikuchi, S., K. Shinpo, S. Tsuji, I. Yabe, M. Niino, and K. Tashiro. 2003. Brefeldin A-induced neurotoxicity in cultured spinal cord neurons. J. Neurosci. Res. 71:591-599.
64. Kinghorn, A. D. 2008. Drug discovery from natural products. In Foye’s Principles of Medicinal Chemistry, 6th edn., eds. T. Lemke and D.A. Williams, pp. 12-25. Baltimore, MD: Wolters Kluwer/Lippincott Williams & Wilkins.
65. Kinghorn, A. D., E. J. Carcache-Blanco, H.-B. Chai, J. Orjala, N. R. Farnsworth, D. D. Soejarto, N. H. Oberlies, M. C. Wani, D. J. Kroll, C. J. Pearce, S. M. Swanson, R. A. Kramer, W. C. Rose, C. R. Fairchild, G. D. Vite, S. Emanuel, D. Jarjoura, and F. O. Cope. 2009. Discovery of anticancer agents of diverse natural origin. Pure Appl. Chem. 81:1051-1063.
66. Kinghorn, A. D., N. R. Farnsworth, D. D. Soejarto, G. A. Cordell, J. M. Pezzuto, G. O. Udeani, M. C. Wani, M. E. Wall, H. A. Navarro, R. A. Kramer, A. T. Menendez, C. R. Fairchild, K. E. Lane, S. Forenza, D. M. Vyas, K. S. Lam, and Y.-Z. Shu. 1999. Novel strategies for the discovery of plant-derived anticancer agents. Pure Appl. Chem. 71:1611-1618.
67. Kinghorn, A. D., N. R. Farnsworth, D. D. Soejarto, G. A. Cordell, S. M. Swanson, J. M. Pezzuto, M. C. Wani, M. E. Wall, N. C. Oberlies, D. J. Kroll, R. A. Kramer, W. C. Rose, G. D. Vite, C. R. Fairchild, R. W. Peterson, and R. Wild. 2003. Novel strategies for the discovery of plant-derived anticancer agents. Pharm. Biol. 41(Suppl.):53-67.
68. Kubbutat, M. H., S. N. Jones, and K. H. Vousden. 1997. Regulation of p53 stability by MDM2. Nature 387:299-303.
69. Li, J. W.-H. and J. C. Vederas. 2009. Drug discovery and natural products: End of an era or an endless frontier? Science 325:161-165.
70. Liang, J., R. E. Moore, E. D. Moher, J. E. Munroe, R. S. Alawar, D. A. Hay, D. L. Varie, T. Y. Zhang, J. A. Aikins, M. J. Martinelli, C. Shih, J. E. Ray, L. L. Gibson, V. Vasudevan, L. Polin, K. White, J. Kushner, C. Simpson, S. Pugh, and T. H. Corbett. 2005. Cryptophycins-309, 249 and other cryptophycin analogs: Preclinical efficacy studies with mouse and human tumors. Invest. New Drugs 23:213-224.
71. Liepa, A. J. 1981. A synthesis of hydroxylated isoflavylium salts and their reduction products. Aust. J. Chem. 34:2647-2655.
72. Lin, Y., S. Schiavo, J. Orjala, P. Vouros, and R. Kautz. 2008. Microscale LC-MS-NMR plat¬form applied to the identification of active cyanobacterial metabolites. Anal. Chem. 80:8045-8054.
73. Luesch, H., R. E. Moore, V. J. Paul, S. L. Mooberry, and T. H. Corbett. 2001. Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total ste¬reochemistry and biological evaluation of its analogue symplostatin 1. J. Nat. Prod. 64:907-910.
74. MacMillan, J., A. E. Vanstone, and S. K. Yeboah. 1972. Fungal products. Part III. Structure of wortmannin and some hydrolysis products. J. Chem. Soc., Perkin Trans. 1:2898-2903.
75. Maki, C. G., J. M. Huibregtse, and P. M. Howley. 1996. In vivo ubiquitination and proteasome-mediated degradation of p53(1). Cancer Res. 56:2649-2654.
76. McAlpine, J. B. 2009. Advances in the understanding and use of the genomic base of micro¬bial secondary metabolite biosynthesis for the discovery of new natural products. J. Nat. Prod. 72:566-572.
77. McCloud, T. G., M. P. Burns, F. D. Majadly, G. M. Muschik, D. A. Miller, K. K. Poole, J. M. Roach, J. T. Ross, and W. B. Lebherz, III. 1995. Production of brefeldin-A. J. Ind. Microbiol. 15:5-9.
78. McMorris, T. C. and M. Anchel. 1963. Structures of basidiomycete metabolites illudin S and illudin M. J. Am. Chem. Soc. 85:831-852.
79. McMorris, T. C., R. Chimmani, M. Gurram, M. D. Staake, and M. J. Kelner. 2007. Synthesis and antitumor activity of amine analogs of irofulven. Bioorg. Med. Chem. Lett. 17:6770-6772.
80. Mi, Q., J. M. Pezzuto, N. R. Farnsworth, M. C. Wani, A. D. Kinghorn, and S. M. Swanson. 2009. Use of the in vivo hollow fiber assay in natural products anticancer drug discov¬ery. J. Nat. Prod. 72:573-580.
81. Misiek, M. and D. Hoffmeister. 2007. Fungal genetics, genomics, and secondary metabolites in pharmaceutical sciences. Planta Med. 73:103-115.
82. Miyase, T., M. Sano, H. Nakai, M. Muraoka, M. Nakazawa, M. Suzuki, K. Yoshino, Y. Nishihara, and J. Tanai. 1999. Antioxidants from Lespedeza homoloba. (I). Phytochemistry 52:303-310.
83. Molinski, T. F. 2009. Nanomole-scale natural products discovery. Curr. Opin. Drug Discov. Dev. 12:197-206.
84. Momand, J., H. H. Wu, and G. Dasgupta. 2000. MDM2-Master regulator of the p53 tumor suppressor protein. Gene 242:15-29.
85. Myers, N., R. A. Mittermeier, G. A. B. Da Fonseca, and J. Kent. 2000. Biodiversity hotspots for conservation priorities. Nature (London) 403:853-858.
86. Nagaoka, Y., K. Otsuki, T. Fujita, and S. Uesato. 2008. Effects of phosphorylation of immuno¬modulatory agent FTY720 (fingolimod) on antiproliferative activity against breast and colon cancer cells. Biol. Pharm. Bull. 31:1177-1181.
87. Naik, R. G., S. L. Kattige, S. V. Bhat, B. Alreja, N. J. De Souza, and R. H. Rupp. 1988. An antiinflammatory and immunomodulatory piperidinylbenzopyranone from Dysoxylum binectariferum: Isolation, structure and total synthesis. Tetrahedron 44:2081-2086.
88. Navon, A. and A. Ciechanover. 2009. The 26S proteasome: From basic mechanisms to drug targeting. J. Biol. Chem. 284:33713-33718.
89. NCI Biological Testing Branch. Hollow fiber assay protocols for tumor cell lines. http://dtp.nci.nih.gov/branches/btb/pdf/cancer_protocol_hollow_fiber.pdf
90. Newman, D. J. and G. M. Cragg. 2004. Marine natural products and related compounds in clinical and advanced preclinical trials. J. Nat. Prod. 67:1216-1238.
91. Newman, D. J. and G. M. Cragg. 2005. Developments and future trends in anticancer natural products drug discovery. In Anticancer Agents from Natural Products, eds. G. M. Cragg, D. G. I. Kingston, and D. J. Newman, pp. 553-571. Boca Raton, FL: CRC/Taylor & Francis.
92. Newman, D. J. and G. M. Cragg. 2007. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod. 70:461-477.
93. Newton, G. G. F. and E. P. Abraham. 1955. Cephalosporin-C, a new antibiotic containing sulphur and d-alpha-aminoadipic acid. Nature 175:548.
94. Nielsen, K. F. and J. Smedsgaard. 2003. Fungal metabolite screening: Database of 474 myco¬toxins and fungal metabolites for dereplication by standardised liquid chromatography-UV-mass spectrometry methodology. J. Chromatogr. A 1002:111-136.
95. Oberlies, N. H. and D. J. Kroll. 2004. Camptothecin and taxol: Historic achievements in natu¬ral products research. J. Nat. Prod. 67:129-135.
96. Paci, A., K. Rezai, A. Deroussent, D. De Valeriola, M. Re, S. Weill, E. Cvitkovic, C. Kahatt, A. Shah, S. Waters, G. Weems, G. Vassal, and F. Lokiec. 2006. Pharmacokinetics, metabolism, and routes of excretion of intravenous irofulven in patients with advanced solid tumors. Drug Metab. Dispos. 34:1918-1926.
97. Pan, L., E. J. Carcache de Blanco, and A. D. Kinghorn. 2009. Plant-derived natural products as leads for drug discovery. In Plant-Derived Natural Products: Synthesis, Function, and Application, eds. A. E. Osbourn and V. Lanzotti, pp. 546-567. New York: Springer.
98. Pearce, C. 1997. Biologically active fungal metabolites. Adv. Appl. Microbiol. 44:1-80.
99. Pearce, C., P. Eckard, I. Gruen-Wollny, and F. G. Hanske. 2010. Microorganisms: Their role in the discovery and development of medicines. In Natural Product Chemistry for Drug Discovery, eds. A. D. Buss and M. S. Butler, pp. 215-244. Cambridge, U.K.: The Royal Society of Chemistry.
100. Pel, H. J., J. H. de Winde, D. B. Archer, P. S. Dyer, G. Hofmann, P. J. Schaap, G. Turner, R. P. de Vries, R. Albang, K. Albermann, M. R. Andersen, J. D. Bendtsen, J. A. E. Benen, M. van den Berg, S. Breestraat, M. X. Caddick, R. Contreras, M. Cornell, P. M. Coutinho, E. G. J. Danchin, A. J. M. Debets, P. Dekker, P. W. M. van Dijck, A. van Dijk, L. Dijkhuizen, A. J. M. Driessen, C. d’Enfert, S. Geysens, C. Goosen, G. S. P. Groot, P. W. J. de Groot, T. Guillemette, B. Henrissat, M. Herweijer, J. P. T. W. van den Hombergh, C. A. M. van den Hondel, R. T. M. van der Heijden, R. M. van der Kaaij, F. M. Klis, H. J. Kools, C. P. Kubicek, P. A. van Kuyk, J. Lauber, X. Lu, M. J. E. C. van der Maarel, R. Meulenberg, H. Menke, M. A. Mortimer, J. Nielsen, S. G. Oliver, M. Olsthoorn, K. Pal, N. N. M. E. van Peij, A. F. J. Ram, U. Rinas, J. A. Roubos, C. M. Sagt, M. Schmoll, J. Sun, D. Ussery, J. Varga, W. Vervecken, P. J. J. van de Vondervoort, H. Wedler, H. A. B. Woesten, A.-P. Zeng, A. J. J. van Ooyen, J. Visser, and H. Stam. 2007. Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88. Nat. Biotechnol. 25:221-231.
101. Perkel, V. S., Y. Miura, and J. A. Magner. 1989. Brefeldin-A inhibits oligosaccharide process¬ing of glycoproteins in mouse hypothyroid pituitary tissue at several subcellular sites. Proc. Soc. Exp. Biol. Med. 190:286-293.
102. Pettit, G. R., G. M. Cragg, D. L. Herald, J. M. Schmidt, and P. Lohavanijaya. 1982. Antineoplastic agents. 84. Isolation and structure of combretastatin. Can. J. Chem. 60:1374-1376.
103. Pettit, G. R., Y. Kamano, C. Dufresne, R. L. Cerny, C. L. Herald, and J. M. Schmidt. 1989a. Isolation and structure of the cytostatic linear depsipeptide dolastatin 15. J. Org. Chem. 54:6005-6006.
104. Pettit, G. R., Y. Kamano, C. L. Herald, A. A. Tuinman, F. E. Boettner, H. Kizu, J. M. Schmidt, L. Baczynskyj, K. B. Tomer, and R. J. Bontems. 1987. The isolation and structure of a remarkable marine animal antineoplastic constituent: Dolastatin 10. J. Am. Chem. Soc. 109:6883-6885.
105. Pettit, G. R., S. B. Singh, E. Hamel, C. M. Lin, D. S. Alberts, and D. Garcia-Kendall. 1989b. Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4. Experientia. 45:209-211.
106. Pickart, C. M. 2004. Back to the future with ubiquitin. Cell 116:181-190.
107. Piekarz, R. L., R. Frye, M. Turner, J. J. Wright, S. L. Allen, M. H. Kirschbaum, J. Zain, H. M. Prince, J. P. Leonard, L. J. Geskin, C. Reeder, D. Joske, W. D. Figg, E. R. Gardner, S. M. Steinberg, E. S. Jaffe, M. Stetler-Stevenson, S. Lade, A. T. Fojo, and S. E. Bates. 2009. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as mono¬therapy for patients with cutaneous T-cell lymphoma. J. Clin. Oncol. 27:5410-5417.
108. Pinney, K. G., C. Jelinek, K. Edvardsen, D. J. Chaplin, and G. R. Pettit. 2005. The discovery and development of the combretastatins. In Anticancer Agents from Natural Products, eds. G. M. Cragg, D. G. I. Kingston, and D. J. Newman, pp. 23-46. Boca Raton, FL: CRC/Taylor & Francis.
109. Powell, R. G., D. Weisleder, and C. R. Smith. 1970. Structures of harringtonine, isoharringto¬nine, and homoharringtonine. Tetrahedron Lett. 11:815-818.
110. Powell, R. G., D. Weisleder, and C. R. Smith. 1972. Antitumor alkaloids from Cephalotaxus harringtonia: Structure and activity. J. Pharm. Sci. 61:1227-1230.
111. Powis, G., M. Berggren, A. Gallegos, T. Frew, S. Hill, A. Kozikowski, R. Bonjouklian, L. Zalkow, R. Abraham, C. Ashendel, R. Shultz, and R. Merriman. 1995. Advances with phospholipid signalling as a target for anticancer drug development. Acta Biochim. Pol. 42:395-403.
112. Pronzato, P. 2008. New therapeutic options for chemotherapy-resistant metastatic breast can¬cer. Drugs 68:139-146.
113. Rae, J. M., S. J. Ramus, M. Waltham, J. E. Armes, I. G. Campbell, R. Clarke, R. J. Barndt, M. D. Johnson, and E. W. Thompson. 2004. Common origins of MDA-MB-435 cells from various sources with those shown to have melanoma properties. Clin. Exp. Metastasis 21:543-552.
114. Rammohan, K. W. and J. Shoemaker. 2010. Emerging multiple sclerosis oral therapies. Neurology 74:S47-S53.
115. Ray, A., T. Okouneva, T. Manna, H. P. Miller, S. Schmid, L. Arthaud, R. Luduena, M. A. Jordan, and L. Wilson. 2007. Mechanism of action of the microtubule-targeted anti¬mitotic depsipeptide tasidotin (formerly ILX651) and its major metabolite tasidotin C-carboxylate. Cancer Res. 67:3767-3776.
116. Rybowicz, J. and C. Gurk-Turner. 2002. Caspofungin: The first agent available in the echino¬candin class of antifungals. Proc. Baylor Univ. Med. Cent. 15:97-99.
117. Saklani, A. and S. K. Kutty. 2008. Plant-derived compounds in clinical trials. Drug Discov. Today 13:161-171.
118. Sashidhara, K. V., K. N. White, and P. Crews. 2009. A selective account of effective paradigms and significant outcomes in the discovery of inspirational marine natural products. J. Nat. Prod. 72:588-602.
119. Satiat-Jeunemaitre, B. and C. Hawes. 1993. The distribution of secretory products in plant cells is affected by brefeldin-A. Cell Biol. Int. 17:183-193.
120. Schopf, J. W. 2000. The fossil record: Tracing the roots of the cyanobacterial lineage. In: The Ecology of Cyanobacteria. Their Diversity in Time and Space, eds. B. A. Whitton and M. Potts, pp. 13-35. Dordrecht, the Netherlands: Kluwer Academic Publishers.
121. Schultz, R. M., R. L. Merriman, S. L. Andis, R. Bonjouklian, G. B. Grindey, P. G. Rutherford, A. Gallegos, K. Massey, and G. Powis. 1995. In vitro and in vivo antitumor activ¬ity of the phosphatidylinositol-3-kinase inhibitor, wortmannin. Anticancer Res. 15:1135-1139.
122. Schwartz, R. E., C. F. Hirsch, D. F. Sesin, J. E. Flor, M. Chartrain, R. E. Fromtling, G. H. Harris, M. J. Salvatore, J. M. Liesch, and K. Yudin. 1990. Pharmaceuticals from cultured algae. J. Ind. Microbiol. 5:113-124.
123. Shaw, G. and P. K. S. Lam. 2007. Health aspects of freshwater cyanobacterial toxins. Water Sci. Technol. Water Supply 7:193-203.
124. Sherr, C. J. and J. D. Weber. 2000. The Arf/p53 pathway. Curr. Opin. Genet. Dev. 10:94-99.
125. Shih, C. and B. A. Teicher. 2001. Cryptophycins: A novel class of potent antimitotic antitumor depsipeptides. Curr. Pharm. Des. 7:1259-1276.
126. Shoemaker, R. H. 2006. The NCI 60 human tumour cell line anticancer drug screen. Nat. Rev. Cancer 6:813-823.
127. Sielaff, H., G. Christiansen, and R. Schwecke. 2006. Natural products from cyanobacteria: Exploiting a new source for drug discovery. IDrugs 9:119-127.
128. Simmons, T. L., E. Andrianasolo, K. McPhail, P. Flatt, and W. H. Gerwick. 2005. Marine natural products as anticancer drugs. Mol. Cancer Ther. 4:333-342.
129. Singh, S., B. N. Kate, and U. C. Banerjee. 2005. Bioactive compounds from cyanobacteria and microalgae: An overview. Crit. Rev. Biotechnol. 25:73-95.
130. Soejarto, D. D., J. A. Tarzien Sorensen, C. Gyllenhaal, G. A. Cordell, N. R. Farnsworth, H. H. S. Fong, A. D. Kinghorn, and J.M. Pezzuto. The evolution of the University of Illinois’ policy on benefit-sharing in research on natural products. 2002. In Ethnobiology and Biocultural Diversity, eds. J. R. Stepp, F. S. Wyndham, and R. Zarger, pp. 21-30. Athens, GA: University of Georgia Press.
131. Soussi, T. 2000. The p53 tumor suppressor gene: From molecular biology to clinical investiga¬tion. Ann. N. Y. Acad. Sci. 910:121-137; discussion 37-39.
132. Su, B. N., B. Y. Hwang, H. Chai, E. J. Carcache-Blanco, L. B. Kardono, J. J. Afriastini, S. Riswan, R. Wild, N. Laing, N. R. Farnsworth, G. A. Cordell, S. M. Swanson, and A. D. Kinghorn. 2004. Activity-guided fractionation of the leaves of Ormosia suma¬trana using a proteasome inhibition assay. J. Nat. Prod. 67:1911-1914.
133. Sullivan, R., J. E. Smith, and N. J. Rowan. 2006. Medicinal mushrooms and cancer therapy-Translating a traditional practice into Western medicine. Perspect. Biol. Med. 49:159-170.
134. Tan, L. T. 2007. Bioactive natural products from marine cyanobacteria for drug discovery. Phytochemistry 68:954-979.
135. Tan, G., C. Gyllenhaal, and D. D. Soejarto. 2007. Biodiversity as a source of anticancer drugs. Curr. Drug Targets 7:265-277.
136. Tkacz, J. S. 1992. Emerging Targets in Antibacterial and Antifungal Chemotherapy, eds. N. H. Georgopapadakou and J. A. Sutcliffe, 606pp. New York: Chapman & Hall.
137. Turgeon, B. G., S. Oide, and K. Bushley. 2008. Creating and screening Cochliobolus heter¬ostrophus non-ribosomal peptide synthetase mutants. Mycol. Res. 112:200-206.
138. Vagelos, P. R. 1991. Are prescription drug prices high? Science 252:1080-1084.
139. van Apeldoorn, M. E., H. P. van Egmond, G. J. A. Speijers, and G. J. I. Bakker. 2007. Toxins of cyanobacteria. Mol. Nutr. Food Res. 51:7-60.
140. Van Laar, E. S., S. Roth, S. Weitman, J. R. MacDonald, and S. J. Waters. 2004. Activity of irofulven against human pancreatic carcinoma cell lines in vitro and in vivo. Anticancer Res. 24:59-65.
141. Versace, R. W. 2003. The silatecans, a novel class of lipophilic camptothecins. Expert Opin. Ther. Patents 13:751-760.
142. Wall, M. E., M. C. Wani, D. M. Brown, F. Fullas, J. B. Oswald, F. F. Josephson, N. M. Thornton, J. M. Pezzuto, C. W. W. Beecher, N. R. Farnsworth, G. A. Cordell, and A. D. Kinghorn. 1996. Effect of tannins on screening of plant extracts for enzyme inhibitory activity and techniques for their removal. Phytomedicine 3:281-285.
143. Wasser, S. P. 2002. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl. Microbiol. Biotechnol. 60:258-274.
144. Weber, G., K. Schorgendorfer, E. Schneider-Scherzer, and E. Leitner. 1994. The peptide syn¬thetase catalyzing cyclosporine production in Tolypocladium niveum is encoded by a giant 45.8-kilobase open reading frame. Curr. Genet. 26:120-125.
145. Welker, M. 2008. Cyanobacterial hepatotoxins: Chemistry, biosynthesis, and occurrence. In Seafood and Freshwater Toxins, 2nd edn., ed. L. M. Botana, pp. 825-843. Boca Raton, FL: CRC Press.
146. Welker, M. and H. von Döhren. 2006. Cyanobacterial peptides-Nature’s own combinatorial biosynthesis. FEMS Microbiol. Rev. 30:530-563.
147. Zhang, M., S. W. Cui, P. C. K. Cheung, and Q. Wang. 2007. Polysaccharides from mushrooms: A review on their isolation process, structural characteristics and antitumor activity. Trends Food Sci. Technol. 18:4-19.
148. Zhu, J. W., H. Hori, H. Nojiri, T. Tsukuda, and Z. Taira. 1997. Synthesis and activity of brefeldin A analogs as inducers of cancer cell differentiation and apoptosis. Bioorg. Med. Chem. Lett. 7:139-144.
149. Zhu, Q., G. Wani, J. Yao, S. Patnaik, Q. E. Wang, M. A. El-Mahdy, M. Praetorius-Ibba, and A. A. Wani. 2007. The ubiquitin-proteasome system regulates p53-mediated transcrip¬tion at p21(Waf1) promoter. Oncogene 26:4199-4208.