BH3 mimetics to improve cancer therapy; mechanisms and examples

Drug Resistance Updates

Volumn 10, Issue 6, 2007, Pages 207-217

  Zhang, Lin ^a   Ming, Lihua ^a   Yu, Jian ^a  

^a UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

Author keywords

ABT 737; Apoptosis; BH3 mimetic; Cancer; Drug resistance

Indexed keywords

2 AMINO 6 BROMO 4 (1 CYANO 2 ETHOXY 2 OXOETHYL) 4H CHROMENE 3 CARBOXYLIC ACID ETHYL ESTER; 4 (3 DIMETHYLAMINO 1 PYRROLIDINYLMETHYL) 3 TRIFLUOROMETHYL N [4 METHYL 3 [[4 (5 PYRIMIDINYL) 2 PYRIMIDINYL]AMINO]PHENYL]BENZAMIDE; 4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; ANTIMYCIN A1; ARABINOSIDE; ASPARAGINASE; BH3 PROTEIN; BORTEZOMIB; CISPLATIN; CYCLOHEXIMIDE; CYCLOPHOSPHAMIDE; DEXAMETHASONE; DOXORUBICIN; ETOPOSIDE; GEFITINIB; GOSSYPOL; IMATINIB; MELPHALAN; NUTLIN 3; OBATOCLAX; PACLITAXEL; PREDNISOLONE; PROTEIN MCL 1; ROSCOVITINE; THALIDOMIDE; TW 37; UNCLASSIFIED DRUG; VINCRISTINE;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; ARTICLE; B CELL LYMPHOMA; CANCER CHEMOTHERAPY; CANCER PATIENT; CANCER THERAPY; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; DRUG EFFECT; DRUG MECHANISM; DRUG POTENTIATION; FOLLICULAR LYMPHOMA; HUMAN; LEUKEMIA CELL; LUNG SMALL CELL CANCER; NONHUMAN; PRIORITY JOURNAL;

AMINO ACID SEQUENCE; ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BCL-X PROTEIN; BIPHENYL COMPOUNDS; DRUG RESISTANCE, NEOPLASM; DRUGS, INVESTIGATIONAL; HUMANS; MOLECULAR SEQUENCE DATA; NEOPLASM PROTEINS; NEOPLASMS; NITROPHENOLS; PIPERAZINES; PROTEIN STRUCTURE, TERTIARY; PROTO-ONCOGENE PROTEINS C-BCL-2; SEQUENCE ALIGNMENT; SULFONAMIDES; TREATMENT OUTCOME;

EID: 38549130324     PISSN: 13687646     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.drup.2007.08.002     Document Type: Article

References (115)

1. Adams J.M., and Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26 (2007) 1324-1337
2. Amundson S.A., Myers T.G., Scudiero D., Kitada S., Reed J.C., and Fornace Jr. A.J. An informatics approach identifying markers of chemosensitivity in human cancer cell lines. Cancer Res. 60 (2000) 6101-6110
3. An J., Chen Y., and Huang Z. Critical upstream signals of cytochrome C release induced by a novel Bcl-2 inhibitor. J. Biol. Chem. 279 (2004) 19133-19140
4. An J., Chervin A.S., Nie A., Ducoff H.S., and Huang Z. Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor. Oncogene 26 (2007) 652-661
5. Anderson J.E., Hansen L.L., Mooren F.C., Post M., Hug H., Zuse A., and Los M. Methods and biomarkers for the diagnosis and prognosis of cancer and other diseases: towards personalized medicine. Drug Resist. Updates 9 (2006) 198-210
6. Baell J.B., and Huang D.C. Prospects for targeting the Bcl-2 family of proteins to develop novel cytotoxic drugs. Biochem. Pharmacol. 64 (2002) 851-863
7. Bauer J.A., Trask D.K., Kumar B., Los G., Castro J., Lee J.S., Chen J., Wang S., Bradford C.R., and Carey T.E. Reversal of cisplatin resistance with a BH3 mimetic, (-)-gossypol, in head and neck cancer cells: role of wild-type p53 and Bcl-xL. Mol. Cancer Ther. 4 (2005) 1096-1104
8. Becattini B., Kitada S., Leone M., Monosov E., Chandler S., Zhai D., Kipps T.J., Reed J.C., and Pellecchia M. Rational design and real time, in-cell detection of the proapoptotic activity of a novel compound targeting Bcl-X(L). Chem. Biol. 11 (2004) 389-395
9. Bernal F., Tyler A.F., Korsmeyer S.J., Walensky L.D., and Verdine G.L. Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. J. Am. Chem. Soc. 129 (2007) 2456-2457
10. Bruncko M., Oost T.K., Belli B.A., et al. Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL. J. Med. Chem. 50 (2007) 641-662
11. Cartron P.F., Gallenne T., Bougras G., Gautier F., Manero F., Vusio P., Meflah K., Vallette F.M., and Juin P. The first alpha helix of Bax plays a necessary role in its ligand-induced activation by the BH3-only proteins Bid and PUMA. Mol. Cell 16 (2004) 807-818
12. Certo M., Del Gaizo Moore V., Nishino M., Wei G., Korsmeyer S., Armstrong S.A., and Letai A. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 9 (2006) 351-365
13. Chan S.L., Lee M.C., Tan K.O., et al. Identification of chelerythrine as an inhibitor of BclXL function. J. Biol. Chem. 278 (2003) 20453-20456
14. Chauhan D., Velankar M., Brahmandam M., et al. A novel Bcl-2/Bcl-X(L)/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma. Oncogene 26 (2007) 2374-2380
15. Chen L., Willis S.N., Wei A., Smith B.J., Fletcher J.I., Hinds M.G., Colman P.M., Day C.L., Adams J.M., and Huang D.C. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol. Cell 17 (2005) 393-403
16. Chen S., Dai Y., Harada H., Dent P., and Grant S. Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation. Cancer Res. 67 (2007) 782-791
17. Cheng E.H., Wei M.C., Weiler S., Flavell R.A., Mak T.W., Lindsten T., and Korsmeyer S.J. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol. Cell 8 (2001) 705-711
18. Cory S., and Adams J.M. Killing cancer cells by flipping the Bcl-2/Bax switch. Cancer Cell 8 (2005) 5-6
19. Dai Y., and Grant S. Targeting multiple arms of the apoptotic regulatory machinery. Cancer Res. 67 (2007) 2908-2911
20. Dai Y., Rahmani M., Corey S.J., Dent P., and Grant S. A Bcr/Abl-independent, Lyn-dependent form of imatinib mesylate (STI-571) resistance is associated with altered expression of Bcl-2. J. Biol. Chem. 279 (2004) 34227-34239
21. Danial N.N., and Korsmeyer S.J. Cell death. Critical control points. Cell 116 (2004) 205-219
22. Degterev A., Lugovskoy A., Cardone M., Mulley B., Wagner G., Mitchison T., and Yuan J. Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nat. Cell Biol. 3 (2001) 173-182
23. Del Gaizo Moore V., Brown J.R., Certo M., Love T.M., Novina C.D., and Letai A. Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737. J. Clin. Invest. 117 (2007) 112-121
24. Demarchi F., and Brancolini C. Altering protein turnover in tumor cells: new opportunities for anti-cancer therapies. Drug Resist. Updates 8 (2005) 359-368
25. Deng J., Carlson N., Takeyama K., Dal Cin P., Shipp M., and Letai A. BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell 12 (2007) 171-185
26. Denicourt C., and Dowdy S.F. Medicine. Targeting apoptotic pathways in cancer cells. Science 305 (2004) 1411-1413
27. Enyedy I.J., Ling Y., Nacro K., et al. Discovery of small-molecule inhibitors of Bcl-2 through structure-based computer screening. J. Med. Chem. 44 (2001) 4313-4324
28. Feng W.Y., Liu F.T., Patwari Y., Agrawal S.G., Newland A.C., and Jia L. BH3-domain mimetic compound BH3I-2' induces rapid damage to the inner mitochondrial membrane prior to the cytochrome c release from mitochondria. Br. J. Haematol. 121 (2003) 332-340
29. Fesik S.W. Promoting apoptosis as a strategy for cancer drug discovery. Nat. Rev. Cancer 5 (2005) 876-885
30. Green D.R., and Kroemer G. The pathophysiology of mitochondrial cell death. Science 305 (2004) 626-629
31. Hanahan D., and Weinberg R.A. The hallmarks of cancer. Cell 100 (2000) 57-70
32. Hao J.H., Yu M., Liu F.T., Newland A.C., and Jia L. Bcl-2 inhibitors sensitize tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by uncoupling of mitochondrial respiration in human leukemic CEM cells. Cancer Res. 64 (2004) 3607-3616
33. Huang D.C., and Strasser A. BH3-only proteins-essential initiators of apoptotic cell death. Cell 103 (2000) 839-842
34. Johnstone R.W., Ruefli A.A., and Lowe S.W. Apoptosis: a link between cancer genetics and chemotherapy. Cell 108 (2002) 153-164
35. Kang M.H., Kang Y.H., Szymanska B., Wilczynska-Kalak U., Sheard M.A., Harned T., Lock R.B., and Reynolds C.P. Activity of vincristine, L-ASP, and dexamethasone against acute lymphoblastic leukemia is enhanced by the BH3-mimetic ABT-737 in vitro and in vivo. Blood (2007) (Epub ahead of print)
36. Kim H., Rafiuddin-Shah M., Tu H.C., Jeffers J.R., Zambetti G.P., Hsieh J.J., and Cheng E.H. Hierarchical regulation of mitochondrion-dependent apoptosis by BCL-2 subfamilies. Nat. Cell Biol. 8 (2006) 1348-1358
37. Kirkin V., Joos S., and Zornig M. The role of Bcl-2 family members in tumorigenesis. Biochim. Biophys. Acta. 1644 (2004) 229-249
38. Kitada S., Leone M., Sareth S., Zhai D., Reed J.C., and Pellecchia M. Discovery, characterization, and structure-activity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteins. J. Med. Chem. 46 (2003) 4259-4264
39. Kline M.P., Rajkumar S.V., Timm M.M., Kimlinger T.K., Haug J.L., Lust J.A., Greipp P.R., and Kumar S. ABT-737, an inhibitor of Bcl-2 family proteins, is a potent inducer of apoptosis in multiple myeloma cells. Leukemia 21 (2007) 1549-1560
40. Kojima K., Konopleva M., Samudio I.J., Schober W.D., Bornmann W.G., and Andreeff M. Concomitant inhibition of MDM2 and Bcl-2 protein function synergistically induce mitochondrial apoptosis in AML. Cell Cycle 5 (2006) 2778-2786
41. Konopleva M., Contractor R., Tsao T., et al. Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer Cell 10 (2006) 375-388
42. Kuroda J., Kimura S., Strasser A., et al. Apoptosis-based dual molecular targeting by INNO-406, a second-generation Bcr-Abl inhibitor, and ABT-737, an inhibitor of antiapoptotic Bcl-2 proteins, against Bcr-Abl-positive leukemia. Cell Death Differ. 14 (2007) 1667-1677
43. Kuroda J., Puthalakath H., Cragg M.S., et al. Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Proc. Natl. Acad. Sci. U.S.A. 103 (2006) 14907-14912
44. Kutzki O., Park H.S., Ernst J.T., Orner B.P., Yin H., and Hamilton A.D. Development of a potent Bcl-x(L) antagonist based on alpha-helix mimicry. J. Am. Chem. Soc. 124 (2002) 11838-11839
45. Kuwana T., Bouchier-Hayes L., Chipuk J.E., Bonzon C., Sullivan B.A., Green D.R., and Newmeyer D.D. BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol. Cell 17 (2005) 525-535
46. Lee E.F., Czabotar P.E., Smith B.J., Deshayes K., Zobel K., Colman P.M., and Fairlie W.D. Crystal structure of ABT-737 complexed with Bcl-x(L): implications for selectivity of antagonists of the Bcl-2 family. Cell Death Differ. (2007) 1711-1713
47. Lei X., Chen Y., Du G., et al. Gossypol induces Bax/Bak-independent activation of apoptosis and cytochrome c release via a conformational change in Bcl-2. FASEB J. 20 (2006) 2147-2149
48. Leone M., Zhai D., Sareth S., Kitada S., Reed J.C., and Pellecchia M. Cancer prevention by tea polyphenols is linked to their direct inhibition of antiapoptotic Bcl-2-family proteins. Cancer Res. 63 (2003) 8118-8121
49. Letai A., Bassik M.C., Walensky L.D., Sorcinelli M.D., Weiler S., and Korsmeyer S.J. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2 (2002) 183-192
50. Li J., Viallet J., and Haura E.B. A small molecule pan-Bcl-2 family inhibitor, GX15-070, induces apoptosis and enhances cisplatin-induced apoptosis in non-small cell lung cancer cells. Cancer Chemother. Pharmacol. (2007) (Epub ahead of print)
51. Lickliter J.D., Cox J., McCarron J., Martinez N.R., Schmidt C.W., Lin H., Nieda M., and Nicol A.J. Small-molecule Bcl-2 inhibitors sensitise tumour cells to immune-mediated destruction. Br. J. Cancer 96 (2007) 600-608
52. Lin X., Morgan-Lappe S., Huang X., Li L., Zakula D.M., Vernetti L.A., Fesik S.W., and Shen Y. 'Seed' analysis of off-target siRNAs reveals an essential role of Mcl-1 in resistance to the small-molecule Bcl-2/Bcl-X(L) inhibitor ABT-737. Oncogene 26 (2007) 3972-3979
53. Maiuri M.C., Le Toumelin G., Criollo A., et al. Functional and physical interaction between Bcl-X(L) and a BH3-like domain in Beclin-1. EMBO J. 26 (2007) 2527-2539
54. Manero F., Gautier F., Gallenne T., Cauquil N., Gree D., Cartron P.F., Geneste O., Gree R., Vallette F.M., and Juin P. The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death. Cancer Res. 66 (2006) 2757-2764
55. Mashima T., and Tsuruo T. Defects of the apoptotic pathway as therapeutic target against cancer. Drug Resist. Updates 8 (2005) 339-343
56. Mason K.D., Carpinelli M.R., Fletcher J.I., et al. Programmed anuclear cell death delimits platelet life span. Cell 128 (2007) 1173-1186
57. Milanesi E., Costantini P., Gambalunga A., Colonna R., Petronilli V., Cabrelle A., Semenzato G., Cesura A.M., Pinard E., and Bernardi P. The mitochondrial effects of small organic ligands of BCL-2: sensitization of BCL-2-overexpressing cells to apoptosis by a pyrimidine-2,4,6-trione derivative. J. Biol. Chem. 281 (2006) 10066-10072
58. Milella M., Estrov Z., Kornblau S.M., et al. Synergistic induction of apoptosis by simultaneous disruption of the Bcl-2 and MEK/MAPK pathways in acute myelogenous leukemia. Blood 99 (2002) 3461-3464
59. Mohammad R.M., Goustin A.S., Aboukameel A., Chen B., Banerjee S., Wang G., Nikolovska-Coleska Z., Wang S., and Al-Katib A. Preclinical studies of TW-37, a new nonpeptidic small-molecule inhibitor of Bcl-2, in diffuse large cell lymphoma xenograft model reveal drug action on both Bcl-2 and Mcl-1. Clin. Cancer Res. 13 (2007) 2226-2235
60. Mohammad R.M., Wang S., Aboukameel A., Chen B., Wu X., Chen J., and Al-Katib A. Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-X(L) [(-)-gossypol] against diffuse large cell lymphoma. Mol. Cancer Ther. 4 (2005) 13-21
61. Mohammad R.M., Wang S., Banerjee S., Wu X., Chen J., and Sarkar F.H. Nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-XL, (-)-Gossypol, enhances biological effect of genistein against BxPC-3 human pancreatic cancer cell line. Pancreas 31 (2005) 317-324
62. Mollinedo F., and Gajate C. Fas/CD95 death receptor and lipid rafts: new targets for apoptosis-directed cancer therapy. Drug Resist. Updates 9 (2006) 51-73
63. Nijhawan D., Fang M., Traer E., Zhong Q., Gao W., Du F., and Wang X. Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes Dev. 17 (2003) 1475-1486
64. Olejniczak E.T., Van Sant C., Anderson M.G., Wang G., Tahir S.K., Sauter G., Lesniewski R., and Semizarov D. Integrative genomic analysis of small-cell lung carcinoma reveals correlates of sensitivity to bcl-2 antagonists and uncovers novel chromosomal gains. Mol. Cancer Res. 5 (2007) 331-339
65. Oliver C.L., Bauer J.A., Wolter K.G., et al. In vitro effects of the BH3 mimetic, (-)-gossypol, on head and neck squamous cell carcinoma cells. Clin. Cancer Res. 10 (2004) 7757-7763
66. Oliver C.L., Miranda M.B., Shangary S., Land S., Wang S., and Johnson D.E. (-)-Gossypol acts directly on the mitochondria to overcome Bcl-2- and Bcl-X(L)-mediated apoptosis resistance. Mol. Cancer Ther. 4 (2005) 23-31
67. Oliver L., Mahe B., Gree R., Vallette F.M., and Juin P. HA14-1, a small molecule inhibitor of Bcl-2, bypasses chemoresistance in leukaemia cells. Leuk. Res. 31 (2007) 859-863
68. Oltersdorf T., Elmore S.W., Shoemaker A.R., et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435 (2005) 677-681
69. Pei X.Y., Dai Y., and Grant S. The proteasome inhibitor bortezomib promotes mitochondrial injury and apoptosis induced by the small molecule Bcl-2 inhibitor HA14-1 in multiple myeloma cells. Leukemia 17 (2003) 2036-2045
70. Pei X.Y., Dai Y., and Grant S. The small-molecule Bcl-2 inhibitor HA14-1 interacts synergistically with flavopiridol to induce mitochondrial injury and apoptosis in human myeloma cells through a free radical-dependent and Jun NH2-terminal kinase-dependent mechanism. Mol. Cancer Ther. 3 (2004) 1513-1524
71. Pellecchia M., and Reed J.C. Inhibition of anti-apoptotic Bcl-2 family proteins by natural polyphenols: new avenues for cancer chemoprevention and chemotherapy. Curr. Pharm. Des. 10 (2004) 1387-1398
72. Perez-Galan P., Roue G., Villamor N., Campo E., and Colomer D. The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak. Blood 109 (2007) 4441-4449
73. Petros A.M., Nettesheim D.G., Wang Y., et al. Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies. Protein Sci. 9 (2000) 2528-2534
74. Ray S., Bucur O., and Almasan A. Sensitization of prostate carcinoma cells to Apo2L/TRAIL by a Bcl-2 family protein inhibitor. Apoptosis 10 (2005) 1411-1418
75. Reed J.C. Apoptosis-targeted therapies for cancer. Cancer Cell 3 (2003) 17-22
76. Reed J.C., and Pellecchia M. Apoptosis-based therapies for hematologic malignancies. Blood 106 (2005) 408-418
77. Sadowsky J.D., Fairlie W.D., Hadley E.B., Lee H.S., Umezawa N., Nikolovska-Coleska Z., Wang S., Huang D.C., Tomita Y., and Gellman S.H. (alpha/beta+alpha)-peptide antagonists of BH3 domain/Bcl-x(L) recognition: toward general strategies for foldamer-based inhibition of protein-protein interactions. J. Am. Chem. Soc. 129 (2007) 139-154
78. Sadowsky J.D., Schmitt M.A., Lee H.S., Umezawa N., Wang S., Tomita Y., and Gellman S.H. Chimeric (alpha/beta+alpha)-peptide ligands for the BH3-recognition cleft of Bcl-XL: critical role of the molecular scaffold in protein surface recognition. J. Am. Chem. Soc. 127 (2005) 11966-11968
79. Sattler M., Liang H., Nettesheim D., et al. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 275 (1997) 983-986
80. Sawyers C.L. Disabling Abl-perspectives on Abl kinase regulation and cancer therapeutics. Cancer Cell 1 (2002) 13-15
81. Schwartz P.S., Manion M.K., Emerson C.B., Fry J.S., Schulz C.M., Sweet I.R., and Hockenbery D.M. 2-Methoxy antimycin reveals a unique mechanism for Bcl-xL inhibition. Mol. Cancer Ther. 6 (2007) 2073-2080
82. Shangary S., and Johnson D.E. Peptides derived from BH3 domains of Bcl-2 family members: a comparative analysis of inhibition of Bcl-2, Bcl-x(L) and Bax oligomerization, induction of cytochrome c release, and activation of cell death. Biochemistry 41 (2002) 9485-9495
83. Shangary S., and Johnson D.E. Recent advances in the development of anticancer agents targeting cell death inhibitors in the Bcl-2 protein family. Leukemia 17 (2003) 1470-1481
84. Shangary S., Oliver C.L., Tillman T.S., Cascio M., and Johnson D.E. Sequence and helicity requirements for the proapoptotic activity of Bax BH3 peptides. Mol. Cancer Ther. 3 (2004) 1343-1354
85. Sinicrope F.A., Penington R.C., and Tang X.M. Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis is inhibited by Bcl-2 but restored by the small molecule Bcl-2 inhibitor, HA 14-1, in human colon cancer cells. Clin. Cancer Res. 10 (2004) 8284-8292
86. Stein R.C., Joseph A.E., Matlin S.A., Cunningham D.C., Ford H.T., and Coombes R.C. A preliminary clinical study of gossypol in advanced human cancer. Cancer Chemother. Pharmacol. 30 (1992) 480-482
87. Tahir S.K., Yang X., Anderson M.G., et al. Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res. 67 (2007) 1176-1183
88. Tortora G., Bianco R., Daniele G., Ciardello F., McCubrey J.A., Ricciardi M.R., et al. Overcoming resistance to molecularly targeted anticancer therapies: rational drug combinations based on EGFR and MAPK inhibition for solid tumors and haematologi malignancies. Drug Resist. Updates 10 (2007) 81-100
89. Trudel S., Li Z.H., Rauw J., Tiedemann R.E., Wen X.Y., and Stewart A.K. Preclinical studies of the pan-Bcl inhibitor obatoclax (GX015-070) in multiple myeloma. Blood 109 (2007) 5430-5438
90. Trudel S., Stewart A.K., Li Z., Shu Y., Liang S.B., Trieu Y., Reece D., Paterson J., Wang D., and Wen X.Y. The Bcl-2 family protein inhibitor, ABT-737, has substantial antimyeloma activity and shows synergistic effect with dexamethasone and melphalan. Clin. Cancer Res. 13 (2007) 621-629
91. Tzung S.P., Kim K.M., Basanez G., Giedt C.D., Simon J., Zimmerberg J., Zhang K.Y., and Hockenbery D.M. Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3. Nat. Cell Biol. 3 (2001) 183-191
92. van Delft M.F., Wei A.H., Mason K.D., et al. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 10 (2006) 389-399
93. Van Poznak C., Seidman A.D., Reidenberg M.M., et al. Oral gossypol in the treatment of patients with refractory metastatic breast cancer: a phase I/II clinical trial. Breast Cancer Res. Treat. 66 (2001) 239-248
94. Verhaegen M., Bauer J.A., Martin de la Vega C., et al. A novel BH3 mimetic reveals a mitogen-activated protein kinase-dependent mechanism of melanoma cell death controlled by p53 and reactive oxygen species. Cancer Res. 66 (2006) 11348-11359
95. Vogelstein B., and Kinzler K.W. Cancer genes and the pathways they control. Nat. Med. 10 (2004) 789-799
96. Vogelstein B., Lane D., and Levine A.J. Surfing the p53 network. Nature 408 (2000) 307-310
97. Walensky L.D., Kung A.L., Escher I., Malia T.J., Barbuto S., Wright R.D., Wagner G., Verdine G.L., and Korsmeyer S.J. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science 305 (2004) 1466-1470
98. Walensky L.D., Pitter K., Morash J., Oh K.J., Barbuto S., Fisher J., Smith E., Verdine G.L., and Korsmeyer S.J. A stapled BID BH3 helix directly binds and activates BAX. Mol. Cell 24 (2006) 199-210
99. Wang X. The expanding role of mitochondria in apoptosis. Genes Dev. 15 (2001) 2922-2933
100. Wang H., Li M., Rhie J.K., Hockenbery D.M., Covey J.M., Zhang R., and Hill D.L. Preclinical pharmacology of 2-methoxyantimycin A compounds as novel antitumor agents. Cancer Chemother. Pharmacol. 56 (2005) 291-298
101. Wang J.L., Liu D., Zhang Z.J., Shan S., Han X., Srinivasula S.M., Croce C.M., Alnemri E.S., and Huang Z. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc. Natl. Acad. Sci. U.S.A. 97 (2000) 7124-7129
102. Wang G., Nikolovska-Coleska Z., Yang C.Y., et al. Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J. Med. Chem. 49 (2006) 6139-6142
103. Willis S.N., Fletcher J.I., Kaufmann T., et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315 (2007) 856-859
104. Wolter K.G., Wang S.J., Henson B.S., Wang S., Griffith K.A., Kumar B., Chen J., Carey T.E., Bradford C.R., and D'Silva N.J. (-)-gossypol inhibits growth and promotes apoptosis of human head and neck squamous cell carcinoma in vivo. Neoplasia 8 (2006) 163-172
105. Xu L., Yang D., Wang S., Tang W., Liu M., Davis M., Chen J., Rae J.M., Lawrence T., and Lippman M.E. (-)-Gossypol enhances response to radiation therapy and results in tumor regression of human prostate cancer. Mol. Cancer Ther. 4 (2005) 197-205
106. Yang T., Kozopas K.M., and Craig R.W. The intracellular distribution and pattern of expression of Mcl-1 overlap with, but are not identical to, those of Bcl-2. J. Cell Biol. 128 (1995) 1173-1184
107. Yeow W.S., Baras A., Chua A., Nguyen D.M., Sehgal S.S., Schrump D.S., and Nguyen D.M. Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J. Thorac. Cardiovasc. Surg. 132 (2006) 1356-1362
108. Yin H., Lee G.I., Sedey K.A., Kutzki O., Park H.S., Orner B.P., Ernst J.T., Wang H.G., Sebti S.M., and Hamilton A.D. Terphenyl-Based Bak BH3 alpha-helical proteomimetics as low-molecular-weight antagonists of Bcl-xL. J. Am. Chem. Soc. 127 (2005) 10191-10196
109. Yu Q. Restoring p53-mediated apoptosis in cancer cells: new opportumities for cancer therapy. Drug Resist. Updates 9 (2006) 19-25
110. Zhai D., Jin C., Satterthwait A.C., and Reed J.C. Comparison of chemical inhibitors of antiapoptotic Bcl-2-family proteins. Cell Death Differ. 13 (2006) 1419-1421
111. Zhang H., Nimmer P.M., Tahir S.K., et al. Bcl-2 family proteins are essential for platelet survival. Cell Death Differ. 14 (2007) 943-951
112. Zhang M., Liu H., Guo R., Ling Y., Wu X., Li B., Roller P.P., Wang S., and Yang D. Molecular mechanism of gossypol-induced cell growth inhibition and cell death of HT-29 human colon carcinoma cells. Biochem. Pharmacol. 66 (2003) 93-103
113. Zhang M., Liu H., Tian Z., Huang J., Remo M., and Li Q.Q. Differential growth inhibition and induction of apoptosis by gossypol between HCT116 and HCT116/Bax(-/-) colorectal cancer cells. Clin. Exp. Pharmacol. Physiol. 34 (2007) 230-237
114. Zhong Q., Gao W., Du F., and Wang X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell 121 (2005) 1085-1095
115. Zong W.X., Lindsten T., Ross A.J., MacGregor G.R., and Thompson C.B. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev. 15 (2001) 1481-1486