Targeting the ubiquitin-proteasome pathway: An emerging concept in cancer therapy

Current Topics in Medicinal Chemistry

Volumn 11, Issue 23, 2011, Pages 2888-2905

  Frezza, Michael ^a   Schmitt, Sara ^a   Dou, Q Ping ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; Bortezomib; Metals; Natural compounds; Nutrition agents; Proteasome

Indexed keywords

APIGENIN; BORTEZOMIB; CARBOPLATIN; CARFILZOMIB; CELASTROL; CEP 18770; CISPLATIN; CLIOQUINOL; CURCUMIN; DEXAMETHASONE; DOCETAXEL; EPIGALLOCATECHIN GALLATE; EPOXOMICIN; FLAVONOID; GEMCITABINE; HYPOXIA INDUCIBLE FACTOR 1; IRINOTECAN; LACTACYSTIN; LENALIDOMIDE; METAL COMPLEX; MLN 9708; PEMETREXED; POLYPHENOL DERIVATIVE; PROTEASOME; PROTEASOME INHIBITOR; QUERCETIN; SALINOSPORAMIDE A; UBIQUITIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORINOSTAT;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BONE MARROW SUPPRESSION; CANCER CELL; CANCER PREVENTION; CANCER RESISTANCE; CANCER SURVIVAL; CANCER THERAPY; CARCINOGENESIS; CATALYSIS; CELL CYCLE PROGRESSION; CELL DEATH; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; CHEMICAL STRUCTURE; DIARRHEA; DOWN REGULATION; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG MEGADOSE; DRUG TOLERABILITY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; FATIGUE; GASTROINTESTINAL IRRITATION; HEMATOLOGIC MALIGNANCY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; LYMPHOMA; MANTLE CELL LYMPHOMA; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NAUSEA; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; OVARY CANCER; OVERALL SURVIVAL; PANCREAS CANCER; PERIPHERAL NEUROPATHY; PROSTATE CANCER; PROTEIN DEGRADATION; PROTEIN SYNTHESIS; PROTEIN TARGETING; SENSORY NEUROPATHY; SIGNAL TRANSDUCTION; SOLID TUMOR; TEA; THROMBOCYTOPENIA; TREATMENT RESPONSE; UPREGULATION;

EID: 83455238007     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/156802611798281311     Document Type: Article

References (196)

1. Adams, J. The development of proteasome inhibitors as anticancer drugs. Cancer Cell, 2004, 5, 417-421.
2. Dou, Q. P.; Smith, D. M.; Daniel, K. G.; Kazi, A. Interruption of tumor cell cycle progression through proteasome inhibition: implications for cancer therapy. Prog. Cell Cycle Res., 2003, 5, 441-446.
3. Landis-Piwowar, K. R.; Milacic, V.; Chen, D.; Yang, H.; Zhao, Y.; Chan, T. H.; Yan, B.; Dou, Q. P. The proteasome as a potential target for novel anticancer drugs and chemosensitizers. Drug Resist. Updat., 2006, 9, 263-273.
4. Dou, Q. P.; Goldfarb, R. H. Bortezomib (millennium pharmaceuticals). IDrugs, 2002, 5, 828-834.
5. Kane, R. C.; Farrell, A. T.; Sridhara, R.; Pazdur, R. United States Food and Drug Administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy. Clin. Cancer Res., 2006, 12, 2955-2960.
6. Berenson, J. R.; Yang, H. H.; Sadler, K.; Jarutirasarn, S. G.; Vescio, R. A.; Mapes, R.; Purner, M.; Lee, S. P.; Wilson, J.; Morrison, B.; Adams, J.; Schenkein, D.; Swift, R. Phase I/II trial assessing bortezomib and melphalan combination therapy for the treatment of patients with relapsed or refractory multiple myeloma. J. Clin. Oncol., 2006, 24, 937-944.
7. Fisher, R. I.; Bernstein, S. H.; Kahl, B. S.; Djulbegovic, B.; Robertson, M. J.; de Vos, S.; Epner, E.; Krishnan, A.; Leonard, J. P.; Lonial, S.; Stadtmauer, E. A.; O'Connor, O. A.; Shi, H.; Boral, A. L.; Goy, A. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J. Clin. Oncol., 2006, 24, 4867-4874.
8. Papandreou, C. N.; Daliani, D. D.; Nix, D.; Yang, H.; Madden, T.; Wang, X.; Pien, C. S.; Millikan, R. E.; Tu, S. M.; Pagliaro, L.; Kim, J.; Adams, J.; Elliott, P.; Esseltine, D.; Petrusich, A.; Dieringer, P.; Perez, C.; Logothetis, C. J. Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. J. Clin. Oncol., 2004, 22, 2108-2121.
9. Chauhan, D.; Hideshima, T.; Anderson, K. C. A novel proteasome inhibitor NPI-0052 as an anticancer therapy. Br. J. Cancer, 2006, 95, 961-965.
10. O'Connor, O. A.; Stewart, A. K.; Vallone, M.; Molineaux, C. J.; Kunkel, L. A.; Gerecitano, J. F.; Orlowski, R. Z. A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies. Clin. Cancer Res., 2009, 15, 7085-7091.
11. Chen, D.; Milacic, V.; Chen, M. S.; Wan, S. B.; Lam, W. H.; Huo, C.; Landis-Piwowar, K. R.; Cui, Q. C.; Wali, A.; Chan, T. H.; Dou, Q. P. Tea polyphenols, their biological effects and potential molecular targets. Histol. Histopathol., 2008, 23, 487-496.
12. Yang, H.; Landis-Piwowar, K. R.; Chen, D.; Milacic, V.; Dou, Q. P. Natural compounds with proteasome inhibitory activity for cancer prevention and treatment. Curr. Protein Pept. Sci., 2008, 9, 227-239.
13. Chen, D.; Milacic, V.; Frezza, M.; Dou, Q. P. Metal complexes, their cellular targets and potential for cancer therapy. Curr. Pharm. Des., 2009, 15, 777-791.
14. Milacic, V.; Fregona, D.; Dou, Q. P. Gold complexes as prospective metal-based anticancer drugs. Histol. Histopathol., 2008, 23, 101-108.
15. Goldberg, A. L. Protein degradation and protection against misfolded or damaged proteins. Nature, 2003, 426, 895-899.
16. Nalepa, G.; Rolfe, M.; Harper, J. W. Drug discovery in the ubiquitin- proteasome system. Nat. Rev. Drug Discov., 2006, 5, 596-613.
17. Orlowski, R. Z.; Kuhn, D. J. Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin. Cancer Res., 2008, 14, 1649-1657.
18. Ciechanover, A.; Orian, A.; Schwartz, A. L. Ubiquitin-mediated proteolysis: biological regulation via destruction. Bioessays, 2000, 22, 442-451.
19. Ciechanover, A. The ubiquitin-proteasome pathway: on protein death and cell life. EMBO J., 1998, 17, 7151-7160.
20. Adams, J. The proteasome: a suitable antineoplastic target. Nat. Rev. Cancer, 2004, 4, 349-360.
21. Peters, J. M.; Cejka, Z.; Harris, J. R.; Kleinschmidt, J. A.; Baumeister, W. Structural features of the 26 S proteasome complex. J. Mol. Biol., 1993, 234, 932-937.
22. Baumeister, W.; Walz, J.; Zuhl, F.; Seemuller, E. The proteasome: paradigm of a self-compartmentalizing protease. Cell, 1998, 92, 367-380.
23. Groll, M.; Ditzel, L.; Lowe, J.; Stock, D.; Bochtler, M.; Bartunik, H. D.; Huber, R. Structure of 20S proteasome from yeast at 2.4 A resolution. Nature, 1997, 386, 463-471.
24. Groll, M.; Heinemeyer, W.; Jager, S.; Ullrich, T.; Bochtler, M.; Wolf, D. H.; Huber, R. The catalytic sites of 20S proteasomes and their role in subunit maturation: a mutational and crystallographic study. Proc. Natl. Acad. Sci. USA, 1999, 96, 10976-10983.
25. DeMartino, G. N.; Slaughter, C. A. The proteasome, a novel protease regulated by multiple mechanisms. J. Biol. Chem., 1999, 274, 22123-22126.
26. Goldberg, A. L.; Cascio, P.; Saric, T.; Rock, K. L. The importance of the proteasome and subsequent proteolytic steps in the generation of antigenic peptides. Mol. Immunol., 2002, 39, 147-164.
27. Coux, O.; Tanaka, K.; Goldberg, A. L. Structure and functions of the 20S and 26S proteasomes. Annu. Rev. Biochem., 1996, 65, 801-847.
28. Nandi, D.; Tahiliani, P.; Kumar, A.; Chandu, D. The ubiquitinproteasome system. J. Biosci., 2006, 31, 137-155.
29. Whitby, F. G.; Masters, E. I.; Kramer, L.; Knowlton, J. R.; Yao, Y.; Wang, C. C.; Hill, C. P. Structural basis for the activation of 20S proteasomes by 11S regulators. Nature, 2000, 408, 115-120.
30. Tanahashi, N.; Yokota, K.; Ahn, J. Y.; Chung, C. H.; Fujiwara, T.; Takahashi, E.; DeMartino, G. N.; Slaughter, C. A.; Toyonaga, T.; Yamamura, K.; Shimbara, N.; Tanaka, K. Molecular properties of the proteasome activator PA28 family proteins and gammainterferon regulation. Genes Cells, 1997, 2, 195-211.
31. Wang, J.; Maldonado, M. A. The ubiquitin-proteasome system and its role in inflammatory and autoimmune diseases. Cell Mol. Immunol., 2006, 3, 255-261.
32. Ossendorp, F.; Fu, N.; Camps, M.; Granucci, F.; Gobin, S. J.; van den Elsen, P. J.; Schuurhuis, D.; Adema, G. J.; Lipford, G. B.; Chiba, T.; Sijts, A.; Kloetzel, P. M.; Ricciardi-Castagnoli, P.; Melief, C. J. Differential expression regulation of the alpha and beta subunits of the PA28 proteasome activator in mature dendritic cells. J. Immunol., 2005, 174, 7815-7822.
33. Hershko, A.; Ciechanover, A. The ubiquitin system. Annu. Rev. Biochem., 1998, 67, 425-479.
34. Schwartz, A. L.; Ciechanover, A. Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Annu. Rev. Pharmacol. Toxicol., 2009, 49, 73-96.
35. Petroski, M. D.; Deshaies, R. J. Mechanism of lysine 48-linked ubiquitin-chain synthesis by the cullin-RING ubiquitin-ligase complex SCF-Cdc34. Cell, 2005, 123, 1107-1120.
36. Adams, J. The proteasome: structure, function, and role in the cell. Cancer Treat. Rev., 2003, 29(Suppl 1), 3-9.
37. Hoyt, M. A.; Coffino, P. Ubiquitin-free routes into the proteasome. Cell Mol. Life Sci., 2004, 61, 1596-1600.
38. Kong, X.; Alvarez-Castelao, B.; Lin, Z.; Castano, J. G.; Caro, J. Constitutive/hypoxic degradation of HIF-alpha proteins by the pro teasome is independent of von Hippel Lindau protein ubiquitylation and the transactivation activity of the protein. J. Biol. Chem., 2007, 282, 15498-15505.
39. Baugh, J. M.; Viktorova, E. G.; Pilipenko, E. V. Proteasomes can degrade a significant proportion of cellular proteins independent of ubiquitination. J. Mol. Biol., 2009, 386, 814-827.
40. Yee Koh, M.; Spivak-Kroizman, T. R.; Powis, G. HIF-1 regulation: not so easy come, easy go. Trends Biochem. Sci., 2008, 33, 526-534.
41. Maxwell, P. H.; Wiesener, M. S.; Chang, G. W.; Clifford, S. C.; Vaux, E. C.; Cockman, M. E.; Wykoff, C. C.; Pugh, C. W.; Maher, E. R.; Ratcliffe, P. J. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature, 1999, 399, 271-275.
42. Smith, L.; Lind, M. J.; Drew, P. J.; Cawkwell, L. The putative roles of the ubiquitin/proteasome pathway in resistance to anticancer therapy. Eur. J. Cancer, 2007, 43, 2330-2338.
43. Dou, Q. P.; Li, B. Proteasome inhibitors as potential novel anticancer agents. Drug Resist. Updat., 1999, 2, 215-223.
44. Loda, M.; Cukor, B.; Tam, S. W.; Lavin, P.; Fiorentino, M.; Draetta, G. F.; Jessup, J. M.; Pagano, M. Increased proteasomedependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat. Med., 1997, 3, 231-234.
45. Li, B.; Dou, Q. P. Bax degradation by the ubiquitin/proteasomedependent pathway: involvement in tumor survival and progression. Proc. Natl. Acad. Sci. USA, 2000, 97, 3850-3855.
46. Kumatori, A.; Tanaka, K.; Inamura, N.; Sone, S.; Ogura, T.; Matsumoto, T.; Tachikawa, T.; Shin, S.; Ichihara, A. Abnormally high expression of proteasomes in human leukemic cells. Proc. Natl. Acad. Sci. USA, 1990, 87, 7071-7075.
47. Almond, J. B.; Cohen, G. M. The proteasome: a novel target for cancer chemotherapy. Leukemia, 2002, 16, 433-443.
48. Sun, J.; Nam, S.; Lee, C. S.; Li, B.; Coppola, D.; Hamilton, A. D.; Dou, Q. P.; Sebti, S. M. CEP1612, a dipeptidyl proteasome inhibitor, induces p21WAF1 and p27KIP1 expression and apoptosis and inhibits the growth of the human lung adenocarcinoma A-549 in nude mice. Cancer Res., 2001, 61, 1280-1284.
49. Yang, H.; Chen, D.; Cui, Q. C.; Yuan, X.; Dou, Q. P. Celastrol, a triterpene extracted from the Chinese Thunder of God Vine, is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res., 2006, 66, 4758-4765.
50. Orlowski, R. Z. The role of the ubiquitin-proteasome pathway in apoptosis. Cell Death Differ., 1999, 6, 303-313.
51. Wojcik, C. Proteasomes in apoptosis: villains or guardians? Cell Mol. Life Sci., 1999, 56, 908-917.
52. McConkey, D. J.; Zhu, K. Mechanisms of proteasome inhibitor action and resistance in cancer. Drug Resist. Updat., 2008, 11, 164-179.
53. Chen, W.; Lee, J.; Cho, S. Y.; Fine, H. A. Proteasome-mediated destruction of the cyclin a/cyclin-dependent kinase 2 complex suppresses tumor cell growth in vitro and in vivo. Cancer Res., 2004, 64, 3949-3957.
54. Diehl, J. A.; Zindy, F.; Sherr, C. J. Inhibition of cyclin D1 phosphorylation on threonine-286 prevents its rapid degradation via the ubiquitin-proteasome pathway. Genes Dev., 1997, 11, 957-972.
55. Won, K. A.; Reed, S. I. Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E. EMBO J., 1996, 15, 4182-4193.
56. Blagosklonny, M. V. P53: an ubiquitous target of anticancer drugs. Int. J. Cancer, 2002, 98, 161-166.
57. Kalejta, R. F.; Shenk, T. Proteasome-dependent, ubiquitinindependent degradation of the Rb family of tumor suppressors by the human cytomegalovirus pp71 protein. Proc. Natl. Acad. Sci. USA, 2003, 100, 3263-3268.
58. Pagano, M.; Tam, S. W.; Theodoras, A. M.; Beer-Romero, P.; Del Sal, G.; Chau, V.; Yew, P. R.; Draetta, G. F.; Rolfe, M. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin- dependent kinase inhibitor p27. Science, 1995, 269, 682-685.
59. Chen, Z. J. Ubiquitin signalling in the NF-kappaB pathway. Nat. Cell Biol., 2005, 7, 758-765.
60. King, R. W.; Deshaies, R. J.; Peters, J. M.; Kirschner, M. W. How proteolysis drives the cell cycle. Science, 1996, 274, 1652-1659.
61. Sherr, C. J.; Roberts, J. M. Inhibitors of mammalian G1 cyclindependent kinases. Genes Dev., 1995, 9, 1149-1163.
62. Sherr, C. J.; Roberts, J. M. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev., 1999, 13, 1501-1512.
63. Deng, C.; Zhang, P.; Harper, J. W.; Elledge, S. J.; Leder, P. Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell, 1995, 82, 675-684.
64. Serrano, M.; Gomez-Lahoz, E.; DePinho, R. A.; Beach, D.; Bar- Sagi, D. Inhibition of ras-induced proliferation and cellular transformation by p16INK4. Science, 1995, 267, 249-252.
65. Katayose, Y.; Kim, M.; Rakkar, A. N.; Li, Z.; Cowan, K. H.; Seth, P. Promoting apoptosis: a novel activity associated with the cyclindependent kinase inhibitor p27. Cancer Res., 1997, 57, 5441-5445.
66. Nickeleit, I.; Zender, S.; Sasse, F.; Geffers, R.; Brandes, G.; Sorensen, I.; Steinmetz, H.; Kubicka, S.; Carlomagno, T.; Menche, D.; Gutgemann, I.; Buer, J.; Gossler, A.; Manns, M. P.; Kalesse, M.; Frank, R.; Malek, N. P. Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition. Cancer Cell, 2008, 14, 23-35.
67. Glotzer, M.; Murray, A. W.; Kirschner, M. W. Cyclin is degraded by the ubiquitin pathway. Nature, 1991, 349, 132-138.
68. Baldin, V.; Cans, C.; Knibiehler, M.; Ducommun, B. Phosphorylation of human CDC25B phosphatase by CDK1-cyclin A triggers its proteasome-dependent degradation. J. Biol. Chem., 1997, 272, 32731-32734.
69. Bernardi, R.; Liebermann, D. A.; Hoffman, B. Cdc25A stability is controlled by the ubiquitin-proteasome pathway during cell cycle progression and terminal differentiation. Oncogene, 2000, 19, 2447-2454.
70. Chen, F.; Zhang, Z.; Bower, J.; Lu, Y.; Leonard, S. S.; Ding, M.; Castranova, V.; Piwnica-Worms, H.; Shi, X. Arsenite-induced Cdc25C degradation is through the KEN-box and ubiquitinproteasome pathway. Proc. Natl. Acad. Sci. USA, 2002, 99, 1990-1995.
71. Chen, Z. J.; Parent, L.; Maniatis, T. Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity. Cell, 1996, 84, 853-862.
72. Palombella, V. J.; Rando, O. J.; Goldberg, A. L.; Maniatis, T. The ubiquitin-proteasome pathway is required for processing the NFkappa B1 precursor protein and the activation of NF-kappa B. Cell, 1994, 78, 773-785.
73. Adams, J. Proteasome inhibition: a novel approach to cancer therapy. Trends Mol. Med., 2002, 8, S49-54.
74. Chen, C.; Edelstein, L. C.; Gelinas, C. The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x(L). Mol. Cell Biol., 2000, 20, 2687-2695.
75. Grumont, R. J.; Rourke, I. J.; Gerondakis, S. Rel-dependent induction of A1 transcription is required to protect B cells from antigen receptor ligation-induced apoptosis. Genes Dev., 1999, 13, 400-411.
76. Wang, C. Y.; Mayo, M. W.; Korneluk, R. G.; Goeddel, D. V.; Baldwin, A. S., Jr. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science, 1998, 281, 1680-1683.
77. Zhou, D.; Brown, S. A.; Yu, T.; Chen, G.; Barve, S.; Kang, B. C.; Thompson, J. S. A high dose of ionizing radiation induces tissuespecific activation of nuclear factor-kappaB in vivo. Radiat. Res., 1999, 151, 703-709.
78. Biswas, D. K.; Iglehart, J. D. Linkage between EGFR family receptors and nuclear factor kappaB (NF-kappaB) signaling in breast cancer. J. Cell Physiol., 2006, 209, 645-652.
79. Chauhan, D.; Uchiyama, H.; Akbarali, Y.; Urashima, M.; Yamamoto, K.; Libermann, T. A.; Anderson, K. C. Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B. Blood, 1996, 87, 1104-1112.
80. Hideshima, T.; Richardson, P.; Chauhan, D.; Palombella, V. J.; Elliott, P. J.; Adams, J.; Anderson, K. C. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res., 2001, 61, 3071-3076.
81. Keats, J. J.; Fonseca, R.; Chesi, M.; Schop, R.; Baker, A.; Chng, W. J.; Van Wier, S.; Tiedemann, R.; Shi, C. X.; Sebag, M.; Braggio, E.; Henry, T.; Zhu, Y. X.; Fogle, H.; Price-Troska, T.; Ahmann, G.; Mancini, C.; Brents, L. A.; Kumar, S.; Greipp, P.; Dispenzieri, A.; Bryant, B.; Mulligan, G.; Bruhn, L.; Barrett, M.; Valdez, R.; Trent, J.; Stewart, A. K.; Carpten, J.; Bergsagel, P. L. Pro miscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer Cell, 2007, 12, 131-144.
82. Hideshima, T.; Ikeda, H.; Chauhan, D.; Okawa, Y.; Raje, N.; Podar, K.; Mitsiades, C.; Munshi, N. C.; Richardson, P. G.; Carrasco, R. D.; Anderson, K. C. Bortezomib induces canonical nuclear factor- kappaB activation in multiple myeloma cells. Blood, 2009, 114, 1046-1052.
83. Cvek, B.; Dvorak, Z. The value of proteasome inhibition in cancer. Can the old drug, disulfiram, have a bright new future as a novel proteasome inhibitor? Drug Discov. Today, 2008, 13, 716-722.
84. An, B.; Goldfarb, R. H.; Siman, R.; Dou, Q. P. Novel dipeptidyl proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent kinase inhibitor p27 and induce apoptosis in transformed, but not normal, human fibroblasts. Cell Death Differ., 1998, 5, 1062-1075.
85. Ma, M. H.; Yang, H. H.; Parker, K.; Manyak, S.; Friedman, J. M.; Altamirano, C.; Wu, Z. Q.; Borad, M. J.; Frantzen, M.; Roussos, E.; Neeser, J.; Mikail, A.; Adams, J.; Sjak-Shie, N.; Vescio, R. A.; Berenson, J. R. The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumor cells to chemotherapeutic agents. Clin Cancer Res., 2003, 9, 1136-1144.
86. Mortenson, M. M.; Schlieman, M. G.; Virudachalam, S.; Lara, P. N.; Gandara, D. G.; Davies, A. M.; Bold, R. J. Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer. Lung Cancer, 2005, 49, 163-170.
87. Voorhees, P. M.; Dees, E. C.; O'Neil, B.; Orlowski, R. Z. The proteasome as a target for cancer therapy. Clin. Cancer Res., 2003, 9, 6316-6325.
88. Green, D. R.; Reed, J. C. Mitochondria and apoptosis. Science, 1998, 281, 1309-1312.
89. Qin, J. Z.; Ziffra, J.; Stennett, L.; Bodner, B.; Bonish, B. K.; Chaturvedi, V.; Bennett, F.; Pollock, P. M.; Trent, J. M.; Hendrix, M. J.; Rizzo, P.; Miele, L.; Nickoloff, B. J. Proteasome inhibitors trigger NOXA-mediated apoptosis in melanoma and myeloma cells. Cancer Res., 2005, 65, 6282-6293.
90. Oda, E.; Ohki, R.; Murasawa, H.; Nemoto, J.; Shibue, T.; Yamashita, T.; Tokino, T.; Taniguchi, T.; Tanaka, N. Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science, 2000, 288, 1053-1058.
91. Adams, J. M.; Cory, S. The Bcl-2 protein family: arbiters of cell survival. Science, 1998, 281, 1322-1326.
92. Nikiforov, M. A.; Riblett, M.; Tang, W. H.; Gratchouck, V.; Zhuang, D.; Fernandez, Y.; Verhaegen, M.; Varambally, S.; Chinnaiyan, A. M.; Jakubowiak, A. J.; Soengas, M. S. Tumor cellselective regulation of NOXA by c-MYC in response to proteasome inhibition. Proc. Natl. Acad. Sci. USA, 2007, 104, 19488-19493.
93. Nencioni, A.; Grunebach, F.; Patrone, F.; Ballestrero, A.; Brossart, P. Proteasome inhibitors: antitumor effects and beyond. Leukemia, 2007, 21, 30-36.
94. Kane, R. C.; Bross, P. F.; Farrell, A. T.; Pazdur, R. Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist, 2003, 8, 508-513.
95. Kane, R. C.; Dagher, R.; Farrell, A.; Ko, C. W.; Sridhara, R.; Justice, R.; Pazdur, R. Bortezomib for the treatment of mantle cell lymphoma. Clin. Cancer Res., 2007, 13, 5291-5294.
96. Adams, J.; Palombella, V. J.; Sausville, E. A.; Johnson, J.; Destree, A.; Lazarus, D. D.; Maas, J.; Pien, C. S.; Prakash, S.; Elliott, P. J. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res., 1999, 59, 2615-2622.
97. Frankel, A.; Man, S.; Elliott, P.; Adams, J.; Kerbel, R. S. Lack of multicellular drug resistance observed in human ovarian and prostate carcinoma treated with the proteasome inhibitor PS-341. Clin. Cancer Res., 2000, 6, 3719-3728.
98. Crawford, L. J.; Walker, B.; Ovaa, H.; Chauhan, D.; Anderson, K. C.; Morris, T. C.; Irvine, A. E. Comparative selectivity and specificity of the proteasome inhibitors BzLLLCOCHO, PS-341, and MG-132. Cancer Res., 2006, 66, 6379-6386.
99. Orlowski, R. Z.; Baldwin, A. S., Jr. NF-kappaB as a therapeutic target in cancer. Trends Mol. Med., 2002, 8, 385-389.
100. Engel, R. H.; Brown, J. A.; Von Roenn, J. H.; O'Regan, R. M.; Bergan, R.; Badve, S.; Rademaker, A.; Gradishar, W. J. A phase II study of single agent bortezomib in patients with metastatic breast cancer: a single institution experience. Cancer Invest., 2007, 25, 733-737.
101. Yang, C. H.; Gonzalez-Angulo, A. M.; Reuben, J. M.; Booser, D. J.; Pusztai, L.; Krishnamurthy, S.; Esseltine, D.; Stec, J.; Broglio, K. R.; Islam, R.; Hortobagyi, G. N.; Cristofanilli, M. Bortezomib (VELCADE) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. Ann. Oncol., 2006, 17, 813-817.
102. Jakob, C.; Egerer, K.; Liebisch, P.; Turkmen, S.; Zavrski, I.; Kuckelkorn, U.; Heider, U.; Kaiser, M.; Fleissner, C.; Sterz, J.; Kleeberg, L.; Feist, E.; Burmester, G. R.; Kloetzel, P. M.; Sezer, O. Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma. Blood, 2007, 109, 2100-2105.
103. Orlowski, R. Z.; Stinchcombe, T. E.; Mitchell, B. S.; Shea, T. C.; Baldwin, A. S.; Stahl, S.; Adams, J.; Esseltine, D. L.; Elliott, P. J.; Pien, C. S.; Guerciolini, R.; Anderson, J. K.; Depcik-Smith, N. D.; Bhagat, R.; Lehman, M. J.; Novick, S. C.; O'Connor, O. A.; Soignet, S. L. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J. Clin. Oncol., 2002, 20, 4420-4427.
104. Jagannath, S.; Barlogie, B.; Berenson, J.; Siegel, D.; Irwin, D.; Richardson, P. G.; Niesvizky, R.; Alexanian, R.; Limentani, S. A.; Alsina, M.; Adams, J.; Kauffman, M.; Esseltine, D. L.; Schenkein, D. P.; Anderson, K. C. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br. J. Haematol., 2004, 127, 165-172.
105. Jagannath, S.; Barlogie, B.; Berenson, J. R.; Siegel, D. S.; Irwin, D.; Richardson, P. G.; Niesvizky, R.; Alexanian, R.; Limentani, S. A.; Alsina, M.; Esseltine, D. L.; Anderson, K. C. Updated survival analyses after prolonged follow-up of the phase 2, multicenter CREST study of bortezomib in relapsed or refractory multiple myeloma. Br. J. Haematol., 2008, 143, 537-540.
106. Richardson, P. G.; Barlogie, B.; Berenson, J.; Singhal, S.; Jagannath, S.; Irwin, D.; Rajkumar, S. V.; Srkalovic, G.; Alsina, M.; Alexanian, R.; Siegel, D.; Orlowski, R. Z.; Kuter, D.; Limentani, S. A.; Lee, S.; Hideshima, T.; Esseltine, D. L.; Kauffman, M.; Adams, J.; Schenkein, D. P.; Anderson, K. C. A phase 2 study of bortezomib in relapsed, refractory myeloma. N. Engl. J. Med., 2003, 348, 2609-2617.
107. Richardson, P. G.; Sonneveld, P.; Schuster, M.; Irwin, D.; Stadtmauer, E.; Facon, T.; Harousseau, J. L.; Ben-Yehuda, D.; Lonial, S.; Goldschmidt, H.; Reece, D.; Miguel, J. S.; Blade, J.; Boccadoro, M.; Cavenagh, J.; Alsina, M.; Rajkumar, S. V.; Lacy, M.; Jakubowiak, A.; Dalton, W.; Boral, A.; Esseltine, D. L.; Schenkein, D.; Anderson, K. C. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood, 2007, 110, 3557-3560.
108. Richardson, P. G.; Sonneveld, P.; Schuster, M. W.; Irwin, D.; Stadtmauer, E. A.; Facon, T.; Harousseau, J. L.; Ben-Yehuda, D.; Lonial, S.; Goldschmidt, H.; Reece, D.; San-Miguel, J. F.; Blade, J.; Boccadoro, M.; Cavenagh, J.; Dalton, W. S.; Boral, A. L.; Esseltine, D. L.; Porter, J. B.; Schenkein, D.; Anderson, K. C. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N. Engl. J. Med., 2005, 352, 2487-2498.
109. Mitsiades, N.; Mitsiades, C. S.; Richardson, P. G.; Poulaki, V.; Tai, Y. T.; Chauhan, D.; Fanourakis, G.; Gu, X.; Bailey, C.; Joseph, M.; Libermann, T. A.; Schlossman, R.; Munshi, N. C.; Hideshima, T.; Anderson, K. C. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. Blood, 2003, 101, 2377-2380.
110. Aghajanian, C.; Dizon, D. S.; Sabbatini, P.; Raizer, J. J.; Dupont, J.; Spriggs, D. R. Phase I trial of bortezomib and carboplatin in recurrent ovarian or primary peritoneal cancer. J. Clin. Oncol., 2005, 23, 5943-5949.
111. Messersmith, W. A.; Baker, S. D.; Lassiter, L.; Sullivan, R. A.; Dinh, K.; Almuete, V. I.; Wright, J. J.; Donehower, R. C.; Carducci, M. A.; Armstrong, D. K. Phase I trial of bortezomib in combination with docetaxel in patients with advanced solid tumors. Clin Cancer Res., 2006, 12, 1270-1275.
112. Ryan, D. P.; O'Neil, B. H.; Supko, J. G.; Rocha Lima, C. M.; Dees, E. C.; Appleman, L. J.; Clark, J.; Fidias, P.; Orlowski, R. Z.; Kashala, O.; Eder, J. P.; Cusack, J. C., Jr. A Phase I study of bortezomib plus irinotecan in patients with advanced solid tumors. Cancer, 2006, 107, 2688-2697.
113. Goy, A.; Younes, A.; McLaughlin, P.; Pro, B.; Romaguera, J. E.; Hagemeister, F.; Fayad, L.; Dang, N. H.; Samaniego, F.; Wang, M.; Broglio, K.; Samuels, B.; Gilles, F.; Sarris, A. H.; Hart, S.; Trehu, E.; Schenkein, D.; Cabanillas, F.; Rodriguez, A. M. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma. J. Clin. Oncol., 2005, 23, 667-675.
114. O'Connor, O. A.; Wright, J.; Moskowitz, C.; Muzzy, J.; MacGregor- Cortelli, B.; Stubblefield, M.; Straus, D.; Portlock, C.; Hamlin, P.; Choi, E.; Dumetrescu, O.; Esseltine, D.; Trehu, E.; Adams, J.; Schenkein, D.; Zelenetz, A. D. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J. Clin. Oncol., 2005, 23, 676-684.
115. Belch, A.; Kouroukis, C. T.; Crump, M.; Sehn, L.; Gascoyne, R. D.; Klasa, R.; Powers, J.; Wright, J.; Eisenhauer, E. A. A phase II study of bortezomib in mantle cell lymphoma: the National Cancer Institute of Canada Clinical Trials Group trial IND.150. Ann. Oncol., 2007, 18, 116-121.
116. Hainsworth, J. D.; Meluch, A. A.; Spigel, D. R.; Barton, J., Jr.; Simons, L.; Meng, C.; Gould, B.; Greco, F. A. Weekly docetaxel and bortezomib as first-line treatment for patients with hormonerefractory prostate cancer: a Minnie Pearl Cancer Research Network phase II trial. Clin. Genitourin. Cancer, 2007, 5, 278-283.
117. Davies, A. M.; Ho, C.; Metzger, A. S.; Beckett, L. A.; Christensen, S.; Tanaka, M.; Lara, P. N.; Lau, D. H.; Gandara, D. R. Phase I study of two different schedules of bortezomib and pemetrexed in advanced solid tumors with emphasis on non-small cell lung cancer. J Thorac. Oncol., 2007, 2, 1112-1116.
118. Alberts, S. R.; Foster, N. R.; Morton, R. F.; Kugler, J.; Schaefer, P.; Wiesenfeld, M.; Fitch, T. R.; Steen, P.; Kim, G. P.; Gill, S. PS-341 and gemcitabine in patients with metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group (NCCTG) randomized phase II study. Ann. Oncol., 2005, 16, 1654-1661.
119. Shah, J. J.; Orlowski, R. Z. Proteasome inhibitors in the treatment of multiple myeloma. Leukemia, 2009, 23, 1964-1979.
120. Oerlemans, R.; Franke, N. E.; Assaraf, Y. G.; Cloos, J.; van Zantwijk, I.; Berkers, C. R.; Scheffer, G. L.; Debipersad, K.; Vojtekova, K.; Lemos, C.; van der Heijden, J. W.; Ylstra, B.; Peters, G. J.; Kaspers, G. L.; Dijkmans, B. A.; Scheper, R. J.; Jansen, G. Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein. Blood, 2008, 112, 2489-2499.
121. Ruckrich, T.; Kraus, M.; Gogel, J.; Beck, A.; Ovaa, H.; Verdoes, M.; Overkleeft, H. S.; Kalbacher, H.; Driessen, C. Characterization of the ubiquitin-proteasome system in bortezomib-adapted cells. Leukemia, 2009, 23, 1098-1105.
122. Joazeiro, C. A.; Anderson, K. C.; Hunter, T. Proteasome inhibitor drugs on the rise. Cancer Res., 2006, 66, 7840-7842.
123. Chauhan, D.; Catley, L.; Li, G.; Podar, K.; Hideshima, T.; Velankar, M.; Mitsiades, C.; Mitsiades, N.; Yasui, H.; Letai, A.; Ovaa, H.; Berkers, C.; Nicholson, B.; Chao, T. H.; Neuteboom, S. T.; Richardson, P.; Palladino, M. A.; Anderson, K. C. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell, 2005, 8, 407-419.
124. Groll, M.; Huber, R.; Potts, B. C. Crystal structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of beta-lactone ring opening and a mechanism for irreversible binding. J. Am. Chem. Soc., 2006, 128, 5136-5141.
125. Chauhan, D.; Singh, A.; Brahmandam, M.; Podar, K.; Hideshima, T.; Richardson, P.; Munshi, N.; Palladino, M. A.; Anderson, K. C. Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma. Blood, 2008, 111, 1654-1664.
126. Chauhan, D.; Singh, A. V.; Ciccarelli, B.; Richardson, P. G.; Palladino, M. A.; Anderson, K. C. Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma. Blood, 2010, 115, 834-845.
127. Sterz, J.; von Metzler, I.; Hahne, J. C.; Lamottke, B.; Rademacher, J.; Heider, U.; Terpos, E.; Sezer, O. The potential of proteasome inhibitors in cancer therapy. Expert Opin. Investig. Drugs, 2008, 17, 879-895.
128. Yang, H.; Zonder, J. A.; Dou, Q. P. Clinical development of novel proteasome inhibitors for cancer treatment. Expert Opin. Investig. Drugs, 2009, 18, 957-971.
129. Kuhn, D. J.; Chen, Q.; Voorhees, P. M.; Strader, J. S.; Shenk, K. D.; Sun, C. M.; Demo, S. D.; Bennett, M. K.; van Leeuwen, F. W.; Chanan-Khan, A. A.; Orlowski, R. Z. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood, 2007, 110, 3281-3290.
130. Demo, S. D.; Kirk, C. J.; Aujay, M. A.; Buchholz, T. J.; Dajee, M.; Ho, M. N.; Jiang, J.; Laidig, G. J.; Lewis, E. R.; Parlati, F.; Shenk, K. D.; Smyth, M. S.; Sun, C. M.; Vallone, M. K.; Woo, T. M.; Molineaux, C. J.; Bennett, M. K. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res., 2007, 67, 6383-6391.
131. Dick, L. R.; Fleming, P. E. Building on bortezomib: secondgeneration proteasome inhibitors as anti-cancer therapy. Drug Discov. Today, 15, 243-249.
132. Kupperman, E.; Lee, E. C.; Cao, Y.; Bannerman, B.; Fitzgerald, M.; Berger, A.; Yu, J.; Yang, Y.; Hales, P.; Bruzzese, F.; Liu, J.; Blank, J.; Garcia, K.; Tsu, C.; Dick, L.; Fleming, P.; Yu, L.; Manfredi, M.; Rolfe, M.; Bolen, J. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res., 70, 1970-1980.
133. Sarkar, F. H.; Li, Y.; Wang, Z.; Kong, D. Cellular signaling perturbation by natural products. Cell Signal., 2009, 21, 1541-1547.
134. Scalbert, A.; Williamson, G. Dietary intake and bioavailability of polyphenols. J. Nutr., 2000, 130, 2073S-2085S.
135. Kemberling, J. K.; Hampton, J. A.; Keck, R. W.; Gomez, M. A.; Selman, S. H. Inhibition of bladder tumor growth by the green tea derivative epigallocatechin-3-gallate. J. Urol., 2003, 170, 773-776.
136. Sartippour, M. R.; Heber, D.; Ma, J.; Lu, Q.; Go, V. L.; Nguyen, M. Green tea and its catechins inhibit breast cancer xenografts. Nutr. Cancer, 2001, 40, 149-156.
137. Shanafelt, T. D.; Lee, Y. K.; Call, T. G.; Nowakowski, G. S.; Dingli, D.; Zent, C. S.; Kay, N. E. Clinical effects of oral green tea extracts in four patients with low grade B-cell malignancies. Leuk. Res., 2006, 30, 707-712.
138. Kavantzas, N.; Chatziioannou, A.; Yanni, A. E.; Tsakayannis, D.; Balafoutas, D.; Agrogiannis, G.; Perrea, D. Effect of green tea on angiogenesis and severity of atherosclerosis in cholesterol-fed rabbit. Vascul. Pharmacol., 2006, 44, 461-463.
139. Kuo, P. L.; Lin, C. C. Green tea constituent (-)-epigallocatechin-3- gallate inhibits Hep G2 cell proliferation and induces apoptosis through p53-dependent and Fas-mediated pathways. J. Biomed. Sci., 2003, 10, 219-227.
140. Zhang, Q.; Tang, X.; Lu, Q.; Zhang, Z.; Rao, J.; Le, A. D. Green tea extract and (-)-epigallocatechin-3-gallate inhibit hypoxia- and serum-induced HIF-1alpha protein accumulation and VEGF expression in human cervical carcinoma and hepatoma cells. Mol. Cancer Ther., 2006, 5, 1227-1238.
141. August, D. A.; Landau, J.; Caputo, D.; Hong, J.; Lee, M. J.; Yang, C. S. Ingestion of green tea rapidly decreases prostaglandin E2 levels in rectal mucosa in humans. Cancer Epidemiol. Biomarkers Prev., 1999, 8, 709-713.
142. Bettuzzi, S.; Brausi, M.; Rizzi, F.; Castagnetti, G.; Peracchia, G.; Corti, A. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a oneyear proof-of-principle study. Cancer Res., 2006, 66, 1234-1240.
143. Jian, L.; Xie, L. P.; Lee, A. H.; Binns, C. W. Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int. J. Cancer, 2004, 108, 130-135.
144. Nakachi, K.; Suemasu, K.; Suga, K.; Takeo, T.; Imai, K.; Higashi, Y. Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn. J. Cancer Res., 1998, 89, 254-261.
145. Golden, E. B.; Lam, P. Y.; Kardosh, A.; Gaffney, K. J.; Cadenas, E.; Louie, S. G.; Petasis, N. A.; Chen, T. C.; Schonthal, A. H. Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood, 2009, 113, 5927-5937.
146. Nam, S.; Smith, D. M.; Dou, Q. P. Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo. J. Biol. Chem., 2001, 276, 13322-13330.
147. Guttridge, D. C.; Albanese, C.; Reuther, J. Y.; Pestell, R. G.; Baldwin, A. S., Jr. NF-kappaB controls cell growth and differentiation through transcriptional regulation of cyclin D1. Mol. Cell Biol., 1999, 19, 5785-5799.
148. Polyak, K.; Lee, M. H.; Erdjument-Bromage, H.; Koff, A.; Roberts, J. M.; Tempst, P.; Massague, J. Cloning of p27Kip1, a cyclin dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell, 1994, 78, 59-66.
149. Kazi, A.; Wang, Z.; Kumar, N.; Falsetti, S. C.; Chan, T. H.; Dou, Q. P. Structure-activity relationships of synthetic analogs of (-)- epigallocatechin-3-gallate as proteasome inhibitors. Anticancer Res., 2004, 24, 943-954.
150. Landis-Piwowar, K. R.; Kuhn, D. J.; Wan, S. B.; Chen, D.; Chan, T. H.; Dou, Q. P. Evaluation of proteasome-inhibitory and apoptosis- inducing potencies of novel (-)-EGCG analogs and their prodrugs. Int. J. Mol. Med., 2005, 15, 735-742.
151. Kuhn, D.; Lam, W. H.; Kazi, A.; Daniel, K. G.; Song, S.; Chow, L. M.; Chan, T. H.; Dou, Q. P. Synthetic peracetate tea polyphenols as potent proteasome inhibitors and apoptosis inducers in human cancer cells. Front. Biosci., 2005, 10, 1010-1023.
152. Landis-Piwowar, K. R.; Wan, S. B.; Wiegand, R. A.; Kuhn, D. J.; Chan, T. H.; Dou, Q. P. Methylation suppresses the proteasomeinhibitory function of green tea polyphenols. J. Cell Physiol., 2007, 213, 252-260.
153. Landis-Piwowar, K. R.; Huo, C.; Chen, D.; Milacic, V.; Shi, G.; Chan, T. H.; Dou, Q. P. A novel prodrug of the green tea polyphenol (-)-epigallocatechin-3-gallate as a potential anticancer agent. Cancer Res., 2007, 67, 4303-4310.
154. Lepley, D. M.; Li, B.; Birt, D. F.; Pelling, J. C. The chemopreventive flavonoid apigenin induces G2/M arrest in keratinocytes. Carcinogenesis, 1996, 17, 2367-2375.
155. Manach, C.; Scalbert, A.; Morand, C.; Remesy, C.; Jimenez, L. Polyphenols: food sources and bioavailability. Am. J. Clin. Nutr., 2004, 79, 727-747.
156. Liu, L. Z.; Fang, J.; Zhou, Q.; Hu, X.; Shi, X.; Jiang, B. H. Apigenin inhibits expression of vascular endothelial growth factor and angiogenesis in human lung cancer cells: implication of chemoprevention of lung cancer. Mol. Pharmacol., 2005, 68, 635-643.
157. Birt, D. F.; Mitchell, D.; Gold, B.; Pour, P.; Pinch, H. C. Inhibition of ultraviolet light induced skin carcinogenesis in SKH-1 mice by apigenin, a plant flavonoid. Anticancer Res., 1997, 17, 85-91.
158. Zheng, P. W.; Chiang, L. C.; Lin, C. C. Apigenin induced apoptosis through p53-dependent pathway in human cervical carcinoma cells. Life Sci., 2005, 76, 1367-1379.
159. Gupta, S.; Afaq, F.; Mukhtar, H. Involvement of nuclear factorkappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells. Oncogene, 2002, 21, 3727-3738.
160. Chen, D.; Daniel, K. G.; Chen, M. S.; Kuhn, D. J.; Landis- Piwowar, K. R.; Dou, Q. P. Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells. Biochem. Pharmacol., 2005, 69, 1421-1432.
161. Chen, D.; Landis-Piwowar, K. R.; Chen, M. S.; Dou, Q. P. Inhibition of proteasome activity by the dietary flavonoid apigenin is associated with growth inhibition in cultured breast cancer cells and xenografts. Breast Cancer Res., 2007, 9, R80.
162. Hertog, M. G.; Hollman, P. C.; Katan, M. B.; Kromhout, D. Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. Nutr. Cancer, 1993, 20, 21-29.
163. Pastrana-Bonilla, E.; Akoh, C. C.; Sellappan, S.; Krewer, G. Phenolic content and antioxidant capacity of muscadine grapes. J. Agric. Food Chem., 2003, 51, 5497-5503.
164. Ueda, H.; Yamazaki, C.; Yamazaki, M. A hydroxyl group of flavonoids affects oral anti-inflammatory activity and inhibition of systemic tumor necrosis factor-alpha production. Biosci. Biotechnol. Biochem., 2004, 68, 119-125.
165. Allison, A. C.; Cacabelos, R.; Lombardi, V. R.; Alvarez, X. A.; Vigo, C. Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2001, 25, 1341-1357.
166. Cleren, C.; Calingasan, N. Y.; Chen, J.; Beal, M. F. Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicity. J. Neurochem., 2005, 94, 995-1004.
167. Somasundaram, S.; Edmund, N. A.; Moore, D. T.; Small, G. W.; Shi, Y. Y.; Orlowski, R. Z. Dietary curcumin inhibits chemotherapy- induced apoptosis in models of human breast cancer. Cancer Res., 2002, 62, 3868-3875.
168. Singh, S.; Khar, A. Biological effects of curcumin and its role in cancer chemoprevention and therapy. Anticancer Agents Med. Chem., 2006, 6, 259-270.
169. Chan, M. M.; Fong, D.; Soprano, K. J.; Holmes, W. F.; Heverling, H. Inhibition of growth and sensitization to cisplatin-mediated killing of ovarian cancer cells by polyphenolic chemopreventive agents. J. Cell Physiol., 2003, 194, 63-70.
170. Chirnomas, D.; Taniguchi, T.; de la Vega, M.; Vaidya, A. P.; Vasserman, M.; Hartman, A. R.; Kennedy, R.; Foster, R.; Mahoney, J.; Seiden, M. V.; D'Andrea, A. D. Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway. Mol. Cancer Ther., 2006, 5, 952-961.
171. Lev-Ari, S.; Strier, L.; Kazanov, D.; Madar-Shapiro, L.; Dvory- Sobol, H.; Pinchuk, I.; Marian, B.; Lichtenberg, D.; Arber, N. Celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells. Clin. Cancer Res., 2005, 11, 6738-6744.
172. Aggarwal, B. B.; Kumar, A.; Bharti, A. C. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res., 2003, 23, 363-398.
173. Milacic, V.; Banerjee, S.; Landis-Piwowar, K. R.; Sarkar, F. H.; Majumdar, A. P.; Dou, Q. P. Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res., 2008, 68, 7283-7292.
174. Wong, E.; Giandomenico, C. M. Current status of platinum-based antitumor drugs. Chem. Rev., 1999, 99, 2451-2466.
175. Eckhardt, S. Recent progress in the development of anticancer agents. Curr. Med. Chem. Anticancer Agents, 2002, 2, 419-439.
176. Galanski, M.; Arion, V. B.; Jakupec, M. A.; Keppler, B. K. Recent developments in the field of tumor-inhibiting metal complexes. Curr. Pharm. Des., 2003, 9, 2078-2089.
177. Galanski, M.; Jakupec, M. A.; Keppler, B. K. Update of the preclinical situation of anticancer platinum complexes: novel design strategies and innovative analytical approaches. Curr. Med. Chem., 2005, 12, 2075-2094.
178. Apelgot, S.; Coppey, J.; Fromentin, A.; Guille, E.; Poupon, M. F.; Roussel, A. Altered distribution of copper (64Cu) in tumor-bearing mice and rats. Anticancer Res., 1986, 6, 159-164.
179. Zowczak, M.; Iskra, M.; Torlinski, L.; Cofta, S. Analysis of serum copper and zinc concentrations in cancer patients. Biol. Trace Elem. Res., 2001, 82, 1-8.
180. Turecky, L.; Kalina, P.; Uhlikova, E.; Namerova, S.; Krizko, J. Serum ceruloplasmin and copper levels in patients with primary brain tumors. Klin. Wochenschr., 1984, 62, 187-189.
181. Kuo, H. W.; Chen, S. F.; Wu, C. C.; Chen, D. R.; Lee, J. H. Serum and tissue trace elements in patients with breast cancer in Taiwan. Biol. Trace Elem. Res., 2002, 89, 1-11.
182. Nayak, S. B.; Bhat, V. R.; Upadhyay, D.; Udupa, S. L. Copper and ceruloplasmin status in serum of prostate and colon cancer patients. Indian J. Physiol. Pharmacol., 2003, 47, 108-110.
183. Diez, M.; Arroyo, M.; Cerdan, F. J.; Munoz, M.; Martin, M. A.; Balibrea, J. L. Serum and tissue trace metal levels in lung cancer. Oncology, 1989, 46, 230-234.
184. Habib, F. K.; Dembinski, T. C.; Stitch, S. R. The zinc and copper content of blood leucocytes and plasma from patients with benign and malignant prostates. Clin. Chim. Acta, 1980, 104, 329-335.
185. Ritchie, C. W.; Bush, A. I.; Masters, C. L. Metal-protein attenuating compounds and Alzheimer's disease. Expert Opin. Investig. Drugs, 2004, 13, 1585-1592.
186. Chen, D.; Cui, Q. C.; Yang, H.; Barrea, R. A.; Sarkar, F. H.; Sheng, S.; Yan, B.; Reddy, G. P.; Dou, Q. P. Clioquinol, a therapeutic agent for Alzheimer's disease, has proteasome-inhibitory, androgen receptor-suppressing, apoptosis-inducing, and antitumor activities in human prostate cancer cells and xenografts. Cancer Res., 2007, 67, 1636-1644.
187. Johansson, B. A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites. Acta. Psychiatr. Scand. Suppl., 1992, 369, 15-26.
188. Vallari, R. C.; Pietruszko, R. Human aldehyde dehydrogenase: mechanism of inhibition of disulfiram. Science, 1982, 216, 637-639.
189. Brar, S. S.; Grigg, C.; Wilson, K. S.; Holder, W. D., Jr.; Dreau, D.; Austin, C.; Foster, M.; Ghio, A. J.; Whorton, A. R.; Stowell, G. W.; Whittall, L. B.; Whittle, R. R.; White, D. P.; Kennedy, T. P. Disulfiram inhibits activating transcription factor/cyclic AMPresponsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease. Mol. Cancer Ther., 2004, 3, 1049-1060.
190. Chen, D.; Cui, Q. C.; Yang, H.; Dou, Q. P. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res., 2006, 66, 10425-10433.
191. Cvek, B. Antabuse (disulfiram) as a pilot case of non-profit drug. Int. J. Cancer, 2010.
192. Ronconi, L.; Marzano, C.; Zanello, P.; Corsini, M.; Miolo, G.; Macca, C.; Trevisan, A.; Fregona, D. Gold(III) dithiocarbamate derivatives for the treatment of cancer: solution chemistry, DNA binding, and hemolytic properties. J. Med. Chem., 2006, 49, 1648-1657.
193. Milacic, V.; Chen, D.; Ronconi, L.; Landis-Piwowar, K. R.; Fregona, D.; Dou, Q. P. A novel anticancer gold(III) dithiocarbamate compound inhibits the activity of a purified 20S proteasome and 26S proteasome in human breast cancer cell cultures and xenografts. Cancer Res., 2006, 66, 10478-10486.
194. Zhang, X.; Frezza, M.; Milacic, V.; Ronconi, L.; Fan, Y.; Bi, C.; Fregona, D.; Dou, Q. P. Inhibition of tumor proteasome activity by gold-dithiocarbamato complexes via both redox-dependent and - independent processes. J. Cell Biochem., 2010, 109, 162-172.
195. Shakya, R.; Peng, F.; Liu, J.; Heeg, M. J.; Verani, C. N. Synthesis, structure, and anticancer activity of gallium(III) complexes with asymmetric tridentate ligands: growth inhibition and apoptosis induction of cisplatin-resistant neuroblastoma cells. Inorg. Chem., 2006, 45, 6263-6268.
196. Chen, D.; Frezza, M.; Shakya, R.; Cui, Q. C.; Milacic, V.; Verani, C. N.; Dou, Q. P. Inhibition of the proteasome activity by gallium(III) complexes contributes to their anti prostate tumor effects. Cancer Res., 2007, 67, 9258-9265.