The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention

Current Protein and Peptide Science

Volumn 11, Issue 6, 2010, Pages 459-470

  Chen, Di ^a   Dou, Q Ping ^a  

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

Author keywords

Anti cancer drugs; Chemotherapy; Proteasome inhibitors; Ubiqitin proteasome pathway

Indexed keywords

ANAPHASE PROMOTING COMPLEX; ANTINEOPLASTIC AGENT; ARSENIC TRIOXIDE; ASCORBIC ACID; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; BORTEZOMIB; CULLIN; CURCUMIN; CYCLIN DEPENDENT KINASE; CYCLOPHOSPHAMIDE; DEXAMETHASONE; DOCETAXEL; DOXORUBICIN; EPICATECHIN; EPIGALLOCATECHIN; EPIGALLOCATECHIN GALLATE; F BOX PROTEIN; FLAVONOID; GENISTEIN; GLIOTOXIN; LACTACYSTIN; MELPHALAN; PROTEASOME; PROTEASOME INHIBITOR; SALINOSPORAMIDE A; THALIDOMIDE; UBIQUITIN; UBIQUITIN PROTEIN LIGASE;

ACUTE GRANULOCYTIC LEUKEMIA; ADVANCED CANCER; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTHRALGIA; ARTICLE; ASTHENIA; BLOOD TOXICITY; BONE MARROW SUPPRESSION; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER PREVENTION; CANCER RESISTANCE; CANCER SURVIVAL; CARCINOGENESIS; CELL CYCLE REGULATION; CELL METABOLISM; CHEMOSENSITIZATION; CHEMOTHERAPY INDUCED EMESIS; COLON TUMOR; CRYSTAL STRUCTURE; DECREASED APPETITE; DIARRHEA; DIZZINESS; DRUG EFFECT; DRUG EFFICACY; DRUG ERUPTION; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG PENETRATION; DRUG TARGETING; DYSPNEA; ENZYME ACTIVITY; ENZYME STRUCTURE; ENZYME SUBSTRATE COMPLEX; ERYTHROPENIA; FACE EDEMA; FATIGUE; GASTROINTESTINAL SYMPTOM; HAND EDEMA; HEMATOLOGIC MALIGNANCY; HERPES ZOSTER; HUMAN; INFECTION; INSOMNIA; KIDNEY CARCINOMA; LEUKOPENIA; LUNG CANCER; LUNG NON SMALL CELL CANCER; MANTLE CELL LYMPHOMA; MESOTHELIOMA; MOLECULARLY TARGETED THERAPY; MULTIPLE MYELOMA; MYALGIA; NAUSEA; NEUROBLASTOMA; NONHODGKIN LYMPHOMA; NONHUMAN; PARESTHESIA; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PROSTATE CANCER; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEINASE INHIBITION; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; SKIN TINGLING; SOLID TUMOR; TEA; THROMBOCYTOPENIA; TUMOR VASCULARIZATION; UBIQUITINATION; WEAKNESS;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL PROLIFERATION; CYSTEINE PROTEINASE INHIBITORS; HUMANS; MODELS, BIOLOGICAL; NEOPLASMS; PROTEASOME ENDOPEPTIDASE COMPLEX; SIGNAL TRANSDUCTION; UBIQUITIN;

EUKARYOTA;

EID: 78651321769     PISSN: 13892037     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920310791824057     Document Type: Article

References (163)

1. Goldberg, A. L. Functions of the proteasome: the lysis at the end ofthe tunnel. Science, 1995, 268, 522-523.
2. Hochstrasser, M. Ubiquitin, proteasomes, and the regulation ofintracellular protein degradation. Curr. Opin. Cell Biol., 1995, 7,215-223.
3. Ciechanover, A. The ubiquitin-proteasome proteolytic pathway. Cell, 1994, 79, 13-21.
4. Orlowski, R. Z.; Dees, E. C. The role of the ubiquitinationproteasomepathway in breast cancer: applying drugs that affect theubiquitin-proteasome pathway to the therapy of breast cancer. Breast Cancer Res., 2003, 5, 1-7.
5. Ciechanover, A. The ubiquitin-proteasome pathway: on proteindeath and cell life. EMBO. J., 1998, 17, 7151-7160.
6. Hideshima, T.; Richardson, P.; Chauhan, D.; Palombella, V. J.; Elliott, P. J.; Adams, J.; Anderson, K. C. The proteasome inhibitorPS-341 inhibits growth, induces apoptosis, and overcomes drugresistance in human multiple myeloma cells. Cancer Res., 2001,61, 3071-3076.
7. Landis-Piwowar, K. R.; Milacic, V.; Chen, D.; Yang, H.; Zhao, Y.; Chan, T. H.; Yan, B.; Dou, Q. P. The proteasome as a potentialtarget for novel anticancer drugs and chemosensitizers. Drug Resist. Update, 2006, 9, 263-273.
8. An, B.; Goldfarb, R. H.; Siman, R.; Dou, Q. P. Novel dipeptidylproteasome inhibitors overcome Bcl-2 protective function andselectively accumulate the cyclin-dependent kinase inhibitor p27and induce apoptosis in transformed, but not normal, humanfibroblasts. Cell Death Differ., 1998, 5, 1062-1075.
9. Lopes, U. G.; Erhardt, P.; Yao, R.; Cooper, G. M. p53-dependentinduction of apoptosis by proteasome inhibitors. J. Biol. Chem., 1997, 272, 12893-12896.
10. Adams, J. Development of the proteasome inhibitor PS-341. Oncologist, 2002, 7, 9-16.
11. Kane, R. C.; Farrell, A. T.; Sridhara, R.; Pazdur, R. United States Food and Drug Administration approval summary: bortezomib forthe treatment of progressive multiple myeloma after one priortherapy. Clin. Cancer Res., 2006, 12, 2955-2960.
12. Neff, N. T.; De Martino, G. N.; Goldberg, A. L. The effect of proteaseinhibitors and decreased temperature on the degradation ofdifferent classes of proteins in cultured hepatocytes. J. Cell Physiol., 1979, 101, 439-457.
13. Etlinger, J. D.; Goldberg, A. L. A soluble ATP-dependent proteolyticsystem responsible for the degradation of abnormalproteins in reticulocytes. Proc. Natl. Acad. Sci. USA, 1977, 74, 54-58.
14. Goldknopf, I. L.; Busch, H. Isopeptide linkage between nonhistoneand histone 2A polypeptides of chromosomal conjugate-proteinA24. Proc. Natl. Acad. Sci. USA, 1977, 74, 864-868.
15. Ciehanover, A.; Hod, Y.; Hershko, A. A heat-stable polypeptidecomponent of an ATP-dependent proteolytic system fromreticulocytes. Biochem. Biophys. Res. Commun., 1978, 81, 1100-1105.
16. Hershko, A.; Ciechanover, A.; Heller, H.; Haas, A. L.; Rose, I. A. Proposed role of ATP in protein breakdown: conjugation of proteinwith multiple chains of the polypeptide of ATP-dependentproteolysis. Proc. Natl. Acad. Sci. USA, 1980, 77, 1783-1786.
17. Hershko, A.; Ciechanover, A.; Rose, I. A. Resolution of the ATPdependentproteolytic system from reticulocytes: a component thatinteracts with ATP. Proc. Natl. Acad. Sci. USA, 1979, 76, 3107-3110.
18. Groll, M.; Bajorek, M.; Kohler, A.; Moroder, L.; Rubin, D. M.; Huber, R.; Glickman, M. H.; Finley, D. A gated channel into theproteasome core particle. Nat. Struct. Biol., 2000, 7, 1062-1067.
19. Kohler, A.; Bajorek, M.; Groll, M.; Moroder, L.; Rubin, D. M.; Huber, R.; Glickman, M. H.; Finley, D. The substrate translocationchannel of the proteasome. Biochimie., 2001, 83, 325-332.
20. Kohler, A.; Cascio, P.; Leggett, D. S.; Woo, K. M.; Goldberg, A. L.; Finley, D. The axial channel of the proteasome core particle isgated by the Rpt2 ATPase and controls both substrate entry andproduct release. Mol. Cell., 2001, 7, 1143-1152.
21. Scheffner, M.; Nuber, U.; Huibregtse, J. M. Protein ubiquitinationinvolving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature, 1995, 373, 81-83.
22. Hochstrasser, M. Ubiquitin-dependent protein degradation. Annu. Rev. Genet., 1996, 30, 405-439.
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 Aresolution. Nature, 1997, 386, 463-471.
24. Hendil, K. B.; Khan, S.; Tanaka, K. Simultaneous binding of PA28and PA700 activators to 20 S proteasomes. Biochem. J., 1998, 332(Pt 3), 749-754.
25. Nalepa, G.; Rolfe, M.; Harper, J. W. Drug discovery in theubiquitin-proteasome system. Nat. Rev. Drug Discov., 2006, 5,596-613.
26. Kopp, F.; Steiner, R.; Dahlmann, B.; Kuehn, L.; Reinauer, H. Sizeand shape of the multicatalytic proteinase from rat skeletal muscle. Biochim. Biophys. Acta., 1986, 872, 253-260.
27. Lowe, J.; Stock, D.; Jap, B.; Zwickl, P.; Baumeister, W.; Huber, R. Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution. Science, 1995, 268, 533-539.
28. Pickart, C. M.; Cohen, R. E. Proteasomes and their kin: proteases inthe machine age. Nat. Rev. Mol. Cell Biol., 2004, 5, 177-187.
29. Nandi, D.; Tahiliani, P.; Kumar, A.; Chandu, D. The ubiquitinproteasomesystem. J. Biosci., 2006, 31, 137-155.
30. Peters, J. M.; Cejka, Z.; Harris, J. R.; Kleinschmidt, J. A.; Baumeister, W. Structural features of the 26 S proteasomecomplex. J. Mol. Biol., 1993, 234, 932-937.
31. Adams, J. The proteasome: a suitable antineoplastic target. Nat. Rev. Cancer, 2004, 4, 349-360.
32. Castro, A.; Bernis, C.; Vigneron, S.; Labbe, J. C.; Lorca, T. Theanaphase-promoting complex: a key factor in the regulation of cellcycle. Oncogene, 2005, 24, 314-325.
33. Escusa, S.; Laporte, D.; Massoni, A.; Boucherie, H.; Dautant, A.; Daignan-Fornier, B. Skp1-Cullin-F-box-dependent degradation ofAah1p requires its interaction with the F-box protein Saf1p. J. Biol. Chem., 2007, 282, 20097-20103.
34. Nakayama, K. I.; Nakayama, K. Ubiquitin ligases: cell-cycle controland cancer. Nat. Rev. Cancer, 2006, 6, 369-381.
35. Bai, C.; Sen, P.; Hofmann, K.; Ma, L.; Goebl, M.; Harper, J. W.; Elledge, S. J. SKP1 connects cell cycle regulators to the ubiquitinproteolysis machinery through a novel motif, the F-box. Cell, 1996,86, 263-274.
36. Skowyra, D.; Craig, K. L.; Tyers, M.; Elledge, S. J.; Harper, J. W. Fboxproteins are receptors that recruit phosphorylated substrates tothe SCF ubiquitin-ligase complex. Cell, 1997, 91, 209-219.
37. Zheng, N.; Schulman, B. A.; Song, L.; Miller, J. J.; Jeffrey, P. D.; Wang, P.; Chu, C.; Koepp, D. M.; Elledge, S. J.; Pagano, M.; Conaway, R. C.; Conaway, J. W.; Harper, J. W.; Pavletich, N. P. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligasecomplex. Nature, 2002, 416, 703-709.
38. Carrano, A. C.; Eytan, E.; Hershko, A.; Pagano, M. SKP2 isrequired for ubiquitin-mediated degradation of the CDK inhibitorp27. Nat. Cell. Biol., 1999, 1, 193-199.
39. Maki, C. G.; Huibregtse, J. M.; Howley, P. M. In vivo ubiquitinationand proteasome-mediated degradation of p53(1). Cancer Res., 1996, 56, 2649-2654.
40. Sdek, P.; Ying, H.; Chang, D. L.; Qiu, W.; Zheng, H.; Touitou, R.; Allday, M. J.; Xiao, Z. X. MDM2 promotes proteasome-dependentubiquitin-independent degradation of retinoblastoma protein. Mol. Cell., 2005, 20, 699-708.
41. Ying, H.; Xiao, Z. X. Targeting retinoblastoma protein fordegradation by proteasomes. Cell Cycle, 2006, 5, 506-508.
42. Wei, W.; Ayad, N. G.; Wan, Y.; Zhang, G. J.; Kirschner, M. W.; Kaelin, W. G., Jr. Degradation of the SCF component Skp2 in cellcyclephase G1 by the anaphase-promoting complex. Nature, 2004,428, 194-198.
43. Chellappan, S. P.; Hiebert, S.; Mudryj, M.; Horowitz, J. M.; Nevins, J. R. The E2F transcription factor is a cellular target for the RBprotein. Cell, 1991, 65, 1053-1061.
44. Harbour, J. W.; Luo, R. X.; Dei Santi, A.; Postigo, A. A.; Dean, D. C. Cdk phosphorylation triggers sequential intramolecular interactionsthat progressively block Rb functions as cells move through G1. Cell, 1999, 98, 859-869.
45. Ayad, N. G.; Rankin, S.; Murakami, M.; Jebanathirajah, J.; Gygi, S.; Kirschner, M. W. Tome-1, a trigger of mitotic entry, is degradedduring G1 via the APC. Cell, 2003, 113, 101-113.
46. Wan, Y.; Liu, X.; Kirschner, M. W. The anaphase-promotingcomplex mediates TGF-beta signaling by targeting Sno N fordestruction. Mol. Cell., 2001, 8, 1027-1039.
47. Wu, G.; Glickstein, S.; Liu, W.; Fujita, T.; Li, W.; Yang, Q.; Duvoisin, R.; Wan, Y. The anaphase-promoting complexcoordinates initiation of lens differentiation. Mol. Biol. Cell, 2007,18, 1018-1029.
48. Bashir, T.; Dorrello, N. V.; Amador, V.; Guardavaccaro, D.; Pagano, M. Control of the SCF(Skp2-Cks1) ubiquitin ligase by theAPC/C(Cdh1) ubiquitin ligase. Nature, 2004, 428, 190-193.
49. Liu, W.; Wu, G.; Li, W.; Lobur, D.; Wan, Y. Cdh1-anaphasepromotingcomplex targets Skp2 for destruction in transforminggrowth factor beta-induced growth inhibition. Mol. Cell Biol., 2007, 27, 2967-2979.
50. Chen, L.; Madura, K. Increased proteasome activity, ubiquitinconjugatingenzymes, and eEF1A translation factor detected inbreast cancer tissue. Cancer Res., 2005, 65, 5599-5606.
51. Kumatori, A.; Tanaka, K.; Inamura, N.; Sone, S.; Ogura, T.; Matsumoto, T.; Tachikawa, T.; Shin, S.; Ichihara, A. Abnormallyhigh expression of proteasomes in human leukemic cells. Proc. Natl. Acad. Sci. USA, 1990, 87, 7071-7075.
52. Li, B.; Dou, Q. P. Bax degradation by the ubiquitin/proteasomedependentpathway: involvement in tumor survival andprogression. Proc. Natl. Acad. Sci. USA, 2000, 97, 3850-3855.
53. Ren, S.; Smith, M. J.; Louro, I. D.; McKie-Bell, P.; Bani, M. R.; Wagner, M.; Zochodne, B.; Redden, D. T.; Grizzle, W. E.; Wang, N.; Smith, D. I.; Herbst, R. A.; Bardenheuer, W.; Opalka, B.; Schutte, J.; Trent, J. M.; Ben-David, Y.; Ruppert, J. M. The p44S10locus, encoding a subunit of the proteasome regulatory particle, isamplified during progression of cutaneous malignant melanoma. Oncogene, 2000, 19, 1419-1427.
54. Goldberg, A. L. Protein degradation and protection againstmisfolded or damaged proteins. Nature, 2003, 426, 895-899.
55. Karin, M.; Cao, Y.; Greten, F. R.; Li, Z. W. NF-kappaB in cancer:from innocent bystander to major culprit. Nat. Rev. Cancer, 2002,2, 301-310.
56. Schubert, U.; Anton, L. C.; Gibbs, J.; Norbury, C. C.; Yewdell, J. W.; Bennink, J. R. Rapid degradation of a large fraction of newlysynthesized proteins by proteasomes. Nature, 2000, 404, 770-774.
57. Wang, C. Y.; Cusack, J. C., Jr.; Liu, R.; Baldwin, A. S., Jr. Control ofinducible chemoresistance: enhanced anti-tumor therapy throughincreased apoptosis by inhibition of NF-kappaB. Nat. Med., 1999,5, 412-417.
58. Zhang, H. G.; Wang, J.; Yang, X.; Hsu, H. C.; Mountz, J. D. Regulation of apoptosis proteins in cancer cells by ubiquitin. Oncogene, 2004, 23, 2009-2015.
59. Adams, J. The development of proteasome inhibitors as anticancerdrugs. Cancer Cell, 2004, 5, 417-421.
60. Chen, D.; Cui, Q. C.; Yang, H.; Dou, Q. P. Disulfiram, a clinicallyused anti-alcoholism drug and copper-binding agent, inducesapoptotic cell death in breast cancer cultures and xenografts viainhibition of the proteasome activity. Cancer Res., 2006, 66, 10425-10433.
61. Chen, D.; Daniel, K. G.; Chen, M. S.; Kuhn, D. J.; Landis-Piwowar, K. R.; Dou, Q. P. Dietary flavonoids as proteasome inhibitors andapoptosis inducers in human leukemia cells. Biochem. Pharmacol., 2005, 69, 1421-1432.
62. Traub, F.; Mengel, M.; Luck, H. J.; Kreipe, H. H.; von Wasielewski, R. Prognostic impact of Skp2 and p27 in human breast cancer. Breast Cancer Res. Treat., 2006, 99, 185-191.
63. Myung, J.; Kim, K. B.; Crews, C. M. The ubiquitin-proteasomepathway and proteasome inhibitors. Med. Res. Rev., 2001, 21, 245-273.
64. Rock, K. L.; Gramm, C.; Rothstein, L.; Clark, K.; Stein, R.; Dick, L.; Hwang, D.; Goldberg, A. L. Inhibitors of the proteasome blockthe degradation of most cell proteins and the generation of peptidespresented on MHC class I molecules. Cell, 1994, 78, 761-771.
65. Dou, Q. P.; Goldfarb, R. H. Bortezomib (millenniumpharmaceuticals). IDrugs, 2002, 5, 828-834.
66. Michaelis, M.; Fichtner, I.; Behrens, D.; Haider, W.; Rothweiler, F.; Mack, A.; Cinatl, J.; Doerr, H. W.; Cinatl, J., Jr. Anti-cancereffects of bortezomib against chemoresistant neuroblastoma celllines in vitro and in vivo. Int. J. Oncol., 2006, 28, 439-446.
67. Sartore-Bianchi, A.; Gasparri, F.; Galvani, A.; Nici, L.; Darnowski, J. W.; Barbone, D.; Fennell, D. A.; Gaudino, G.; Porta, C.; Mutti, L. Bortezomib inhibits nuclear factor-kappaB dependent survival andhas potent in vivo activity in mesothelioma. Clin. Cancer Res., 2007, 13, 5942-5951.
68. Teicher, B. A.; Ara, G.; Herbst, R.; Palombella, V. J.; Adams, J. Theproteasome inhibitor PS-341 in cancer therapy. Clin. Cancer Res., 1999, 5, 2638-2645.
69. Williams, S.; Pettaway, C.; Song, R.; Papandreou, C.; Logothetis, C.; McConkey, D. J. Differential effects of the proteasome inhibitorbortezomib on apoptosis and angiogenesis in human prostate tumorxenografts. Mol. Cancer Ther., 2003, 2, 835-843.
70. Jagannath, S.; Durie, B. G.; Wolf, J.; Camacho, E.; Irwin, D.; Lutzky, J.; McKinley, M.; Gabayan, E.; Mazumder, A.; Schenkein, D.; Crowley, J. Bortezomib therapy alone and in combination withdexamethasone for previously untreated symptomatic multiplemyeloma. Br. J. Haematol., 2005, 129, 776-783.
71. Orlowski, R. Z.; Voorhees, P. M.; Garcia, R. A.; Hall, M. D.; Kudrik, F. J.; Allred, T.; Johri, A. R.; Jones, P. E.; Ivanova, A.; Van Deventer, H. W.; Gabriel, D. A.; Shea, T. C.; Mitchell, B. S.; Adams, J.; Esseltine, D. L.; Trehu, E. G.; Green, M.; Lehman, M. J.; Natoli, S.; Collins, J. M.; Lindley, C. M.; Dees, E. C. Phase 1 trial of theproteasome inhibitor bortezomib and pegylated liposomaldoxorubicin in patients with advanced hematologic malignancies. Blood, 2005, 105, 3058-3065.
72. 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.; Limen-tani, S. A.; Lee, S.; Hideshima, T.; Esseltine, D. L.; Kauffman, M.; Adams, J.; Schenkein, D. P.; Anderson, K. C. A phase 2 study ofbortezomib in relapsed, refractory myeloma. N. Engl. J. Med., 2003, 348, 2609-2617.
73. Orlowski, M.; Wilk, S. Catalytic activities of the 20 S proteasome, a multicatalytic proteinase complex. Arch. Biochem. Biophys., 2000, 383, 1-16.
74. Omura, S.; Fujimoto, T.; Otoguro, K.; Matsuzaki, K.; Moriguchi, R.; Tanaka, H.; Sasaki, Y. Lactacystin, a novel microbialmetabolite, induces neuritogenesis of neuroblastoma cells. J. Antibiot. (Tokyo), 1991, 44, 113-116.
75. Fenteany, G.; Standaert, R. F.; Lane, W. S.; Choi, S.; Corey, E. J.; Schreiber, S. L. Inhibition of proteasome activities and subunitspecificamino-terminal threonine modification by lactacystin. Science, 1995, 268, 726-731.
76. Dick, L. R.; Cruikshank, A. A.; Grenier, L.; Melandri, F. D.; Nunes, S. L.; Stein, R. L. Mechanistic studies on the inactivation of theproteasome by lactacystin: a central role for clasto-lactacystin betalactone. J. Biol. Chem., 1996, 271, 7273-7276.
77. Kupfahl, C.; Ruppert, T.; Dietz, A.; Geginat, G.; Hof, H. Candidaspecies fail to produce the immunosuppressive secondarymetabolite gliotoxin in vitro. FEMS. Yeast Res., 2007, 7, 986-992.
78. Pahl, H. L.; Krauss, B.; Schulze-Osthoff, K.; Decker, T.; Traenckner, E. B.; Vogt, M.; Myers, C.; Parks, T.; Warring, P.; Muhlbacher, A.; Czernilofsky, A. P.; Baeuerle, P. A. Theimmunosuppressive fungal metabolite gliotoxin specificallyinhibits transcription factor NF-kappaB. J. Exp. Med., 1996, 183, 1829-1840.
79. Kroll, M.; Arenzana-Seisdedos, F.; Bachelerie, F.; Thomas, D.; Friguet, B.; Conconi, M. The secondary fungal metabolite gliotoxintargets proteolytic activities of the proteasome. Chem. Biol., 1999,6, 689-698.
80. Reed, J. C. Mechanisms of apoptosis avoidance in cancer. Curr. Opin. Oncol., 1999, 11, 68-75.
81. Wang, X. The expanding role of mitochondria in apoptosis. Genes Dev, 2001, 15, 2922-2933.
82. Budd, R. C. Death receptors couple to both cell proliferation andapoptosis. J. Clin. Invest., 2002, 109, 437-441.
83. Chaudhary, P. M.; Eby, M.; Jasmin, A.; Bookwalter, A.; Murray, J.; Hood, L. Death receptor 5, a new member of the TNFR family, andDR4 induce FADD-dependent apoptosis and activate the NFkappa Bpathway. Immunity, 1997, 7, 821-830.
84. Nagata, S. Fas ligand-induced apoptosis. Annu. Rev. Genet., 1999,33, 29-55.
85. Friedman, J.; Xue, D. To live or die by the sword: the regulation ofapoptosis by the proteasome. Dev. Cell, 2004, 6, 460-461.
86. Orlowski, R. Z. The role of the ubiquitin-proteasome pathway inapoptosis. Cell Death Differ., 1999, 6, 303-313.
87. Fang, S.; Jensen, J. P.; Ludwig, R. L.; Vousden, K. H.; Weissman, A. M. Mdm2 is a RING finger-dependent ubiquitin protein ligasefor itself and p53. J. Biol. Chem., 2000, 275, 8945-8951.
88. Huang, H.; Regan, K. M.; Wang, F.; Wang, D.; Smith, D. I.; vanDeursen, J. M.; Tindall, D. J. Skp2 inhibits FOXO1 in tumorsuppression through ubiquitin-mediated degradation. Proc. Natl. Acad. Sci. USA, 2005, 102, 1649-1654.
89. Yang, T.; Buchan, H. L.; Townsend, K. J.; Craig, R. W. MCL-1, amember of the BLC-2 family, is induced rapidly in response tosignals for cell differentiation or death, but not to signals for cellproliferation. J. Cell Physiol., 1996, 166, 523-536.
90. Zhong, Q.; Gao, W.; Du, F.; Wang, X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1and regulates apoptosis. Cell, 2005, 121, 1085-1095.
91. Perkins, N. D. Integrating cell-signalling pathways with NF-kappaBand IKK function. Nat. Rev. Mol. Cell Biol., 2007, 8, 49-62.
92. Hsu, Y. T.; Wolter, K. G.; Youle, R. J. Cytosol-to-membraneredistribution of Bax and Bcl-X(L) during apoptosis. Proc. Natl. Acad. Sci. USA, 1997, 94, 3668-3672.
93. Dewson, G.; Snowden, R. T.; Almond, J. B.; Dyer, M. J.; Cohen, G. M. Conformational change and mitochondrial translocation ofBax accompany proteasome inhibitor-induced apoptosis of chroniclymphocytic leukemic cells. Oncogene, 2003, 22, 2643-2654.
94. Le Blanc, H.; Lawrence, D.; Varfolomeev, E.; Totpal, K.; Morlan, J.; Schow, P.; Fong, S.; Schwall, R.; Sinicropi, D.; Ashkenazi, A. Tumor-cell resistance to death receptor--induced apoptosis throughmutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat. Med., 2002, 8, 274-281.
95. Walczak, H.; Krammer, P. H. The CD95 (APO-1/Fas) and theTRAIL (APO-2L) apoptosis systems. Exp. Cell Res., 2000, 256,58-66.
96. Orlowski, R. Z.; Baldwin, A. S., Jr. NF-kappaB as a therapeutictarget in cancer. Trends Mol. Med., 2002, 8, 385-389.
97. Winston, J. T.; Strack, P.; Beer-Romero, P.; Chu, C. Y.; Elledge, S. J.; Harper, J. W. The SCFbeta-TRCP-ubiquitin ligase complexassociates specifically with phosphorylated destruction motifs inIkappa Balpha and beta-catenin and stimulates Ikappa Balphaubiquitination in vitro. Genes Dev., 1999, 13, 270-283.
98. Biswas, D. K.; Iglehart, J. D. Linkage between EGFR familyreceptors and nuclear factor kappaB (NF-kappaB) signaling inbreast cancer. J. Cell Physiol., 2006, 209, 645-652.
99. Coffin, J. D.; Poole, T. J. Embryonic vascular development:immunohistochemical identification of the origin and subsequentmorphogenesis of the major vessel primordia in quail embryos. Development, 1988, 102, 735-748.
100. Mitchell, K.; Szekeres, C.; Milano, V.; Svenson, K. B.; Nilsen-Hamilton, M.; Kreidberg, J. A.; Di Persio, C. M. Alpha3beta1integrin in epidermis promotes wound angiogenesis andkeratinocyte-to-endothelial-cell crosstalk through the induction ofMRP3. J. Cell Sci., 2009, 122, 1778-1787.
101. Folkman, J. Angiogenesis in cancer, vascular, rheumatoid and otherdisease. Nat. Med., 1995, 1, 27-31.
102. Crowther, M.; Brown, N. J.; Bishop, E. T.; Lewis, C. E. Microenvironmental influence on macrophage regulation ofangiogenesis in wounds and malignant tumors. J. Leukoc. Biol., 2001, 70, 478-490.
103. Maisonpierre, P. C.; Suri, C.; Jones, P. F.; Bartunkova, S.; Wiegand, S. J.; Radziejewski, C.; Compton, D.; McClain, J.; Aldrich, T. H.; Papadopoulos, N.; Daly, T. J.; Davis, S.; Sato, T. N.; Yancopoulos, G. D. Angiopoietin-2, a natural antagonist for Tie2 that disrupts invivo angiogenesis. Science, 1997, 277, 55-60.
104. Yoshida, S.; Ono, M.; Shono, T.; Izumi, H.; Ishibashi, T.; Suzuki, H.; Kuwano, M. Involvement of interleukin-8, vascular endothelialgrowth factor, and basic fibroblast growth factor in tumor necrosisfactor alpha-dependent angiogenesis. Mol. Cell Biol., 1997, 17, 4015-4023.
105. Ferrara, N.; Davis-Smyth, T. The biology of vascular endothelialgrowth factor. Endocr. Rev., 1997, 18, 4-25.
106. Veikkola, T.; Karkkainen, M.; Claesson-Welsh, L.; Alitalo, K. Regulation of angiogenesis via vascular endothelial growth factorreceptors. Cancer Res., 2000, 60, 203-212.
107. Carmeliet, P.; Ng, Y. S.; Nuyens, D.; Theilmeier, G.; Brusselmans, K.; Cornelissen, I.; Ehler, E.; Kakkar, V. V.; Stalmans, I.; Mattot, V.; Perriard, J. C.; Dewerchin, M.; Flameng, W.; Nagy, A.; Lupu, F.; Moons, L.; Collen, D.; D'Amore, P. A.; Shima, D. T. Impairedmyocardial angiogenesis and ischemic cardiomyopathy in micelacking the vascular endothelial growth factor isoforms VEGF164and VEGF188. Nat. Med., 1999, 5, 495-502.
108. Plate, K. H.; Breier, G.; Weich, H. A.; Risau, W. Vascularendothelial growth factor is a potential tumour angiogenesis factorin human gliomas in vivo. Nature, 1992, 359, 845-848.
109. Shweiki, D.; Itin, A.; Soffer, D.; Keshet, E. Vascular endothelialgrowth factor induced by hypoxia may mediate hypoxia-initiatedangiogenesis. Nature, 1992, 359, 843-845.
110. Pollmann, C.; Huang, X.; Mall, J.; Bech-Otschir, D.; Naumann, M.; Dubiel, W. The constitutive photomorphogenesis 9 signalosomedirects vascular endothelial growth factor production in tumorcells. Cancer Res., 2001, 61, 8416-8421.
111. Ravi, R.; Mookerjee, B.; Bhujwalla, Z. M.; Sutter, C. H.; Artemov, D.; Zeng, Q.; Dillehay, L. E.; Madan, A.; Semenza, G. L.; Bedi, A. Regulation of tumor angiogenesis by p53-induced degradation ofhypoxia-inducible factor 1alpha. Genes Dev., 2000, 14, 34-44.
112. Shibata, A.; Nagaya, T.; Imai, T.; Funahashi, H.; Nakao, A.; Seo, H. Inhibition of NF-kappaB activity decreases the VEGF mRNAexpression in MDA-MB-231 breast cancer cells. Breast Cancer Res. Treat., 2002, 73, 237-243.
113. Strayhorn, W. D.; Wadzinski, B. E. A novel in vitro assay fordeubiquitination of I kappa B alpha. Arch. Biochem. Biophys., 2002, 400, 76-84.
114. Meteoglu, I.; Erdogdu, I. H.; Meydan, N.; Erkus, M.; Barutca, S. NF-Kappa B expression correlates with apoptosis and angiogenesisin clear cell renal cell carcinoma tissues. J. Exp. Clin. Cancer Res., 2008, 27, 53.
115. Huang, S.; Robinson, J. B.; Deguzman, A.; Bucana, C. D.; Fidler, I. J. Blockade of nuclear factor-kappaB signaling inhibitsangiogenesis and tumorigenicity of human ovarian cancer cells bysuppressing expression of vascular endothelial growth factor andinterleukin 8. Cancer Res., 2000, 60, 5334-5339.
116. Adams, J. Preclinical and clinical evaluation of proteasomeinhibitor PS-341 for the treatment of cancer. Curr. Opin. Chem. Biol., 2002, 6, 493-500.
117. Le Blanc, R.; Catley, L. P.; Hideshima, T.; Lentzsch, S.; Mitsiades, C. S.; Mitsiades, N.; Neuberg, D.; Goloubeva, O.; Pien, C. S.; Adams, J.; Gupta, D.; Richardson, P. G.; Munshi, N. C.; Anderson, K. C. Proteasome inhibitor PS-341 inhibits human myeloma cellgrowth in vivo and prolongs survival in a murine model. Cancer Res., 2002, 62, 4996-5000.
118. Nawrocki, S. T.; Bruns, C. J.; Harbison, M. T.; Bold, R. J.; Gotsch, B. S.; Abbruzzese, J. L.; Elliott, P.; Adams, J.; McConkey, D. J. Effects of the proteasome inhibitor PS-341 on apoptosis andangiogenesis in orthotopic human pancreatic tumor xenografts. Mol. Cancer Ther., 2002, 1, 1243-1253.
119. Sunwoo, J. B.; Chen, Z.; Dong, G.; Yeh, N.; Crowl Bancroft, C.; Sausville, E.; Adams, J.; Elliott, P.; Van Waes, C. Novelproteasome inhibitor PS-341 inhibits activation of nuclear factorkappaB, cell survival, tumor growth, and angiogenesis insquamous cell carcinoma. Clin. Cancer Res., 2001, 7, 1419-1428.
120. Huanjie, Y.; Zonder, J. A.; Ping, D. Q. Expert Opinion onInvestigational Drugs, 2009, 18, 957-971.
121. Orlowski, R. Z. The ubiquitin proteasome pathway from bench tobedside. Hematol. Am. Soc. Hematol. Educ. Prog., 2005, 220-225.
122. 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 inhibitorbortezomib in patients with advanced solid tumors withobservations in androgen-independent prostate cancer. J. Clin. Oncol., 2004, 22, 2108-2121.
123. Anderson, K. C.; Kyle, R. A.; Dalton, W. S.; Landowski, T.; Shain, K.; Jove, R.; Hazlehurst, L.; Berenson, J. Multiple Myeloma: New Insights and Therapeutic Approaches. Hematol. Am. Soc. Hematol. Educ. Program., 2000, 147-165.
124. Richardson, P. G.; Hideshima, T.; Anderson, K. C. Bortezomib (PS-341): a novel, first-in-class proteasome inhibitor for the treatmentof multiple myeloma and other cancers. Cancer Control, 2003, 10,361-369.
125. Delic, J.; Masdehors, P.; Omura, S.; Cosset, J. M.; Dumont, J.; Binet, J. L.; Magdelenat, H. The proteasome inhibitor lactacystininduces apoptosis and sensitizes chemo-and radioresistant humanchronic lymphocytic leukaemia lymphocytes to TNF-alphainitiatedapoptosis. Br. J. Cancer, 1998, 77, 1103-1107.
126. Masdehors, P.; Omura, S.; Merle-Beral, H.; Mentz, F.; Cosset, J. M.; Dumont, J.; Magdelenat, H.; Delic, J. Increased sensitivity ofCLL-derived lymphocytes to apoptotic death activation by theproteasome-specific inhibitor lactacystin. Br. J. Haematol., 1999,105, 752-757.
127. Nix D, P. C., Newman R, et al. Clinical development of aproteasome inhibitor, PS-341, for the treatment of cancer. Proc. Annu. Meet. Am. Soc. Clin. Oncol., 2001, 20, 339.
128. Oakervee, H. E.; Popat, R.; Curry, N.; Smith, P.; Morris, C.; Drake, M.; Agrawal, S.; Stec, J.; Schenkein, D.; Esseltine, D. L.; Cavenagh, J. D. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patientswith multiple myeloma. Br. J. Haematol., 2005, 129, 755-762.
129. 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 orhigh-dose dexamethasone for relapsed multiple myeloma. N. Engl. J. Med., 2005, 352, 2487-2498.
130. Curran, M. P.; McKeage, K. Bortezomib: a review of its use inpatients with multiple myeloma. Drugs, 2009, 69, 859-888.
131. 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 teapolyphenols block the anticancer effects of bortezomib and otherboronic acid-based proteasome inhibitors. Blood, 2009, 113, 5927-5937.
132. Kim, T. Y.; Park, J.; Oh, B.; Min, H. J.; Jeong, T. S.; Lee, J. H.; Suh, C.; Cheong, J. W.; Kim, H. J.; Yoon, S. S.; Park, S. B.; Lee, D. S. Natural polyphenols antagonize the antimyeloma activity ofproteasome inhibitor bortezomib by direct chemical interaction. Br. J. Haematol., 2009, 146, 270-281.
133. Liu, F. T.; Agrawal, S. G.; Movasaghi, Z.; Wyatt, P. B.; Rehman, I. U.; Gribben, J. G.; Newland, A. C.; Jia, L. Dietary flavonoidsinhibit the anticancer effects of the proteasome inhibitorbortezomib. Blood, 2008, 112, 3835-3846.
134. Perrone, G.; Hideshima, T.; Ikeda, H.; Okawa, Y.; Calabrese, E.; Gorgun, G.; Santo, L.; Cirstea, D.; Raje, N.; Chauhan, D.; Baccarani, M.; Cavo, M.; Anderson, K. C. Ascorbic acid inhibitsantitumor activity of bortezomib in vivo. Leukemia, 2009, 23, 1679-1686.
135. 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.
136. Shah, M. H.; Young, D.; Kindler, H. L.; Webb, I.; Kleiber, B.; Wright, J.; Grever, M. Phase II study of the proteasome inhibitorbortezomib (PS-341) in patients with metastatic neuroendocrinetumors. Clin. Cancer Res., 2004, 10, 6111-6118.
137. Kondagunta, G. V.; Drucker, B.; Schwartz, L.; Bacik, J.; Marion, S.; Russo, P.; Mazumdar, M.; Motzer, R. J. Phase II trial ofbortezomib for patients with advanced renal cell carcinoma. J. Clin. Oncol., 2004, 22, 3720-3725.
138. Orlowski, R. Z.; Nagler, A.; Sonneveld, P.; Blade, J.; Hajek, R.; Spencer, A.; San Miguel, J.; Robak, T.; Dmoszynska, A.; Horvath, N.; Spicka, I.; Sutherland, H. J.; Suvorov, A. N.; Zhu-ang, S. H.; Parekh, T.; Xiu, L.; Yuan, Z.; Rackoff, W.; Harousseau, J. L. Randomized phase III study of pegylated liposomal doxorubicinplus bortezomib compared with bortezomib alone in relapsed orrefractory multiple myeloma: combination therapy improves timeto progression. J. Clin. Oncol., 2007, 25, 3892-3901.
139. 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 assessingbortezomib and melphalan combination therapy for the treatment ofpatients with relapsed or refractory multiple myeloma. J. Clin. Oncol., 2006, 24, 937-944.
140. Popat, R.; Oakervee, H.; Williams, C.; Cook, M.; Craddock, C.; Basu, S.; Singer, C.; Harding, S.; Foot, N.; Hallam, S.; Odeh, L.; Joel, S.; Cavenagh, J. Bortezomib, low-dose intravenousmelphalan, and dexamethasone for patients with relapsed multiplemyeloma. Br. J. Haematol., 2009, 144, 887-894.
141. Reece, D. E.; Rodriguez, G. P.; Chen, C.; Trudel, S.; Kukreti, V.; Mikhael, J.; Pantoja, M.; Xu, W.; Stewart, A. K. Phase I-II trial ofbortezomib plus oral cyclophosphamide and prednisone in relapsedand refractory multiple myeloma. J. Clin. Oncol., 2008, 26, 4777-4783.
142. Kropff, M.; Bisping, G.; Schuck, E.; Liebisch, P.; Lang, N.; Hentrich, M.; Dechow, T.; Kroger, N.; Salwender, H.; Metzner, B.; Sezer, O.; Engelhardt, M.; Wolf, H. H.; Einsele, H.; Volpert, S.; Heinecke, A.; Berdel, W. E.; Kienast, J. Bortezomib in combinationwith intermediate-dose dexamethasone and continuous low-doseoral cyclophosphamide for relapsed multiple myeloma. Br. J. Haematol., 2007, 138, 330-337.
143. Terpos, E.; Kastritis, E.; Roussou, M.; Heath, D.; Christoulas, D.; Anagnostopoulos, N.; Eleftherakis-Papaiakovou, E.; Tsionos, K.; Croucher, P.; Dimopoulos, M. A. The combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide is aneffective regimen for relapsed/refractory myeloma and isassociated with improvement of abnormal bone metabolism andangiogenesis. Leukemia, 2008, 22, 2247-2256.
144. Berenson, J. R.; Matous, J.; Swift, R. A.; Mapes, R.; Morrison, B.; Yeh, H. S. A phase I/II study of arsenic trioxide/ bortezomib/ascorbic acid combination therapy for the treatment of relapsed orrefractory multiple myeloma. Clin. Cancer Res., 2007, 13, 1762-1768.
145. Fanucchi, M. P.; Fossella, F. V.; Belt, R.; Natale, R.; Fidias, P.; Carbone, D. P.; Govindan, R.; Raez, L. E.; Robert, F.; Ribeiro, M.; Akerley, W.; Kelly, K.; Limentani, S. A.; Crawford, J.; Reimers, H. J.; Axelrod, R.; Kashala, O.; Sheng, S.; Schiller, J. H. Randomized phase II study of bortezomib alone and bortezomib incombination with docetaxel in previously treated advanced nonsmall-cell lung cancer. J. Clin. Oncol., 2006, 24, 5025-5033.
146. Nam, S.; Smith, D. M.; Dou, Q. P. Ester bond-containing teapolyphenols potently inhibit proteasome activity in vitro and invivo. J. Biol. Chem., 2001, 276, 13322-13330.
147. Smith, D. M.; Daniel, K. G.; Wang, Z.; Guida, W. C.; Chan, T. H.; Dou, Q. P. Docking studies and model development of teapolyphenol proteasome inhibitors: applications to rational drugdesign. Proteins, 2004, 54, 58-70.
148. Smith, D. M.; Wang, Z.; Kazi, A.; Li, L. H.; Chan, T. H.; Dou, Q. P. Synthetic analogs of green tea polyphenols as proteasomeinhibitors. Mol. Med., 2002, 8, 382-392.
149. Kuroda, Y.; Hara, Y. Antimutagenic and anticarcinogenic activityof tea polyphenols. Mutat. Res., 1999, 436, 69-97.
150. Kida, K.; Suzuki, M.; Matsumoto, N.; Nanjo, F.; Hara, Y. Identification of biliary metabolites of (-)-epigallocatechin gallatein rats. J. Agric. Food Chem., 2000, 48, 4151-4155.
151. Spencer, J. P. Metabolism of tea flavonoids in the gastrointestinaltract. J. Nutr., 2003, 133, 3255S-3261S.
152. Landis-Piwowar, K. R.; Kuhn, D. J.; Wan, S. B.; Chen, D.; Chan, T. H.; Dou, Q. P. Evaluation of proteasome-inhibitory andapoptosis-inducing potencies of novel (-)-EGCG analogs and theirprodrugs. Int. J. Mol. Med., 2005, 15, 735-742.
153. Kuhn, D.; Lam, W. H.; Kazi, A.; Daniel, K. G.; Song, S.; Chow, L. M.; Chan, T. H.; Dou, Q. P. Synthetic peracetate tea polyphenolsas potent proteasome inhibitors and apoptosis inducers in humancancer cells. Front Biosci., 2005, 10, 1010-1023.
154. 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.
155. Kuhad, A.; Pilkhwal, S.; Sharma, S.; Tirkey, N.; Chopra, K. Effectof curcumin on inflammation and oxidative stress in cisplatininducedexperimental nephrotoxicity. J. Agric. Food Chem., 2007,55, 10150-10155.
156. Singh, S.; Khar, A. Biological effects of curcumin and its role incancer chemoprevention and therapy. Anticancer Agents Med. Chem., 2006, 6, 259-270.
157. Milacic, V.; Banerjee, S.; Landis-Piwowar, K. R.; Sarkar, F. H.; Majumdar, A. P.; Dou, Q. P. Curcumin inhibits the proteasomeactivity in human colon cancer cells in vitro and in vivo. Cancer Res., 2008, 68, 7283-7292.
158. Kazi, A.; Daniel, K. G.; Smith, D. M.; Kumar, N. B.; Dou, Q. P. Inhibition of the proteasome activity, a novel mechanismassociated with the tumor cell apoptosis-inducing ability ofgenistein. Biochem. Pharmacol., 2003, 66, 965-976.
159. Feling, R. H.; Buchanan, G. O.; Mincer, T. J.; Kauffman, C. A.; Jensen, P. R.; Fenical, W. Salinosporamide A: a highly cytotoxicproteasome inhibitor from a novel microbial source, a marinebacterium of the new genus salinospora. Angew. Chem. Int. Ed. Engl., 2003, 42, 355-357.
160. Ma, G.; Nguyen, H.; Romo, D. Concise total synthesis of (+/-)-salinosporamide A, (+/-)-cinnabaramide A, and derivatives via abis-cyclization process: implications for a biosynthetic pathway?Org. Lett., 2007, 9, 2143-2146.
161. Chauhan, D.; Hideshima, T.; Anderson, K. C. A novel proteasomeinhibitor NPI-0052 as an anticancer therapy. Br. J. Cancer., 2006,95, 961-965.
162. 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 novelorally active proteasome inhibitor induces apoptosis in multiplemyeloma cells with mechanisms distinct from Bortezomib. Cancer Cell, 2005, 8, 407-419.
163. Hofmeister, C. C.; Richardson, P.; Zimmerman, T. Clinical trial ofthe novel structure proteasome inhibitor NPI-0052 in patients withrelapsed and relapsed/refractory multiple myeloma (r/r MM). Journal of Clinical Oncology, (2009 ASCO Annual Meeting Proceedings Post-Meeting Edition), 2009, 27, Abstract No. 8505.