Small-molecule Bcl-2 antagonists as targeted therapy in oncology

Current Oncology

Volumn 15, Issue 6, 2008, Pages 2-7

  Warr, M R ^b   Shore, Gordon C ^a  

^a MCGILL UNIVERSITY   (Canada)

^b NONE

Author keywords

Apoptosis; Bcl 2

Indexed keywords

4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; ABT 263; ANTINEOPLASTIC AGENT; BIM PROTEIN; BORTEZOMIB; CISPLATIN; CYCLOPHOSPHAMIDE; CYTARABINE; DEXAMETHASONE; ETOPOSIDE; FLUDARABINE; GOSSYPOL; OBATOCLAX; PACLITAXEL; PROTEIN BAX; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MCL 1; RITUXIMAB; SARCOLYSIN; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; APOPTOSIS; B CELL LYMPHOMA; BREAST CARCINOMA; CELL SURVIVAL; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; COLON CANCER; DRUG ACTIVITY; DRUG PROTEIN BINDING; DRUG TARGETING; HEMATOLOGIC MALIGNANCY; HODGKIN DISEASE; HUMAN; LUNG NON SMALL CELL CANCER; LYMPHOMA; MANTLE CELL LYMPHOMA; MULTIPLE MYELOMA; NONHUMAN; ONCOLOGY; PROSTATE CANCER; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; REVIEW; SOLID TUMOR; UPREGULATION; UTERINE CERVIX CANCER;

EID: 68749112763     PISSN: None     EISSN: 17187729     Source Type: Journal    
DOI: 10.3747/co.v15i6.392     Document Type: Review

References (55)

1. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 200;100:57-70.
2. Alnemri ES, Livingston DJ, Nicholson DW, et al. Human Ice/Ced-3 protease nomenclature. Cell 1996;87:171.
3. Thornberry NA, Lazebnik Y. Caspases: Enemies within. Science 1998;281:1312-16.
4. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998;281:1309-12.
5. Adams JM, Cory S. The Bcl-2 protein family: Arbiters of cell survival. Science 1998;281:1322-6.
6. Breckenridge DG, Germain M, Mathai JP, Nguyen M, Shore GC. Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 2003;22:8608-18.
7. Danial NN, Korsmeyer SJ. Cell death: Critical control points. Cell 2004;116:205-19.
8. Gross A, McDonnell JM, Korsmeyer SJ. Bcl-2 family members and the mitochondria in apoptosis. Genes Dev 1999;13:1899-911.
9. Wei MC, Zong WX, Cheng EH, et al. Proapoptotic Bax and Bak: A requisite gateway to mitochondrial dysfunction and death. Science 2001;292:727-30.
10. Lindsten T, Ross AJ, King A, et al. The combined functions of proapoptotic Bcl-2 family members Bak and Bax are essential for normal development of multiple tissues. Mol Cell 2000;6:1389-99.
11. Huang DCS, Strasser A. BH3-only proteins - essential initiators of apoptotic cell death. Cell 2000;103:839-42.
12. Muchmore SW, Sattler M, Liang H, et al. X-Ray and NMR structure of human Bcl-xl, an inhibitor of programmed cell death. Nature 1996;381:335-41.
13. Sattler M, Liang H, Nettesheim D, et al. Structure of Bcl-xl- Bak peptide complex: Recognition between regulators of apoptosis. Science 1997;275:983-6.
14. Certo M, Del Gaizo Moore V, Nishino M, et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic Bcl-2 family members. Cancer Cell 2006;9:351-65.
15. Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell 2002;2:183-92.
16. Kim H, Rafiuddin-Shah M, Tu HC, et al. Hierarchical regulation of mitochondrion-dependent apoptosis by Bcl-2 subfamilies. Nat Cell Biol 2006;8:1348-58.
17. Willis SN, Fletcher JI, Kaufmann T, et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 2007;315:856-9.
18. Chipuk JE, Green DR. How do Bcl-2 proteins induce mitochondrial outer membrane permeabilization? Trends Cell Biol 2008;18:157-64.
19. Willis SN, Chen L, Dewson G, et al. Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xl, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev 2005;19:1294-305.
20. Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the Bcl-2 gene in human follicular lymphoma. Science 1985;228:1440-3.
21. Reed JC. Dysregulation of apoptosis in cancer. J Clin Oncol 1999;17:2941-53.
22. Reed JC, Pellecchia M. Apoptosis-based therapies for hematologic malignancies. Blood 2005;106:408-18.
23. Shore GC, Viallet J. Modulating the Bcl-2 family of apoptosis suppressors for potential therapeutic benefit in cancer. Hematology Am Soc Hematol Educ Program 2005:226-30.
24. Nguyen M, Marcellus RC, Roulston A, et al. Small molecule obatoclax (GX15-070) antagonizes Mcl-1 and overcomes Mcl-1-mediated resistance to apoptosis. Proc Natl Acad Sci U S A 2007;104:19512-17.
25. Zhai D, Jin C, Satterthwait AC, Reed JC. Comparison of chemical inhibitors of antiapoptotic Bcl-2-family proteins. Cell Death Differ 2006;13:1419-21.
26. Pérez-Galán P, Roué G, López-Guerra M, et al. Bcl-2 phosphorylation modulates sensitivity to the BH3 mimetic GX15-070 (obatoclax) and reduces its synergistic interaction with bortezomib in chronic lymphocytic leukemia cells. Leukemia 2008;22:1712-20.
27. Li J, Viallet J, Haura EB. 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 2008;61:525-34.
28. Campàs C, Cosialls AM, Barragán M, et al. Bcl-2 inhibitors induce apoptosis in chronic lymphocytic leukemia cells. Exp Hematol 2006;34:1663-9.
29. Pérez-Galán P, Roué G, Villamor N, Campo E, Colomer D. The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak. Blood 2007; 109:4441-9.
30. Trudel S, Li ZH, Rauw J, Tiedemann RE, Wen XY, Stewart AK. Preclinical studies of the pan-Bcl inhibitor obatoclax (GX015-070) in multiple myeloma. Blood 2007;109:5430-8.
31. Konopleva M, Watt J, Contractor R, et al. Mechanisms of antileukemic activity of the novel Bcl-2 homology domain-3 mimetic GX15-070 (obatoclax). Cancer Res 2008;68:3413-20.
32. Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005;435:677-81.
33. 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 2007;26:2374-80.
34. Kline MP, Rajkumar SV, Timm MM, et al. ABT-737, an inhibitor of Bcl-2 family proteins, is a potent inducer of apoptosis in multiple myeloma cells. Leukemia 2007;21:1549-60.
35. 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 2006;10:375-88.
36. Del Gaizo Moore V, Schlis KD, Sallan SE, Armstrong SA, Letai A. Bcl-2 dependence and ABT-737 sensitivity in acute lymphoblastic leukemia. Blood 2008;111:2300-9.
37. Trudel S, Stewart AK, Li Z, et al. The Bcl-2 family protein inhibitor, ABT-737, has substantial antimyeloma activity and shows synergistic effect with dexamethasone and melphalan. Clin Cancer Res 2007;13:621-9.
38. Del Gaizo Moore V, Brown JR, Certo M, Love TM, Novina CD, Letai A. Chronic lymphocytic leukemia requires Bcl2 to sequester prodeath Bim, explaining sensitivity to Bcl2 antagonist ABT-737. J Clin Invest 2007;117:112-21.
39. Tse C, Shoemaker AR, Adickes J, et al. ABT-263: A potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 2008;68:3421-8.
40. Wang G, Nikolovska-Coleska Z, Yang CY, et al. Structurebased design of potent small-molecule inhibitors of antiapoptotic Bcl-2 proteins. J Med Chem 2006;49:6139-42.
41. Balakrishnan K, Wierda WG, Keating MJ, Gandhi V. Gossypol, a BH3 mimetic, induces apoptosis in chronic lymphocytic leukemia cells. Blood 2008;112:1971-80.
42. Meng Y, Tang W, Dai Y, et al. Natural BH3 mimetic (-)-gossypol chemosensitizes human prostate cancer via Bcl-xl inhibition accompanied by increase of Puma and Noxa. Mol Cancer Ther 2008;7:2192-202.
43. Kline MP, Rajkumar SV, Timm MM, et al. R-(-)-Gossypol (AT-101) activates programmed cell death in multiple myeloma cells. Exp Hematol 2008;36:568-76.
44. Zhang M, Liu H, Tian Z, Griffith BN, Ji M, Li QQ. Gossypol induces apoptosis in human PC-3 prostate cancer cells by modulating caspase-dependent and caspase-independent cell death pathways. Life Sci 2007;80:767-74.
45. Mohammad RM, Wang S, Aboukameel A, et al. Preclinical studies of a nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-x(l) [(-)-gossypol] against diffuse large cell lymphoma. Mol Cancer Ther 2005;4:13-21.
46. Zhang M, Liu H, Guo R, et al. Molecular mechanism of gossy pol-induced cell growth inhibition and cell death of HT-29 human colon carcinoma cells. Biochem Pharmacol 2003;66:93-103.
47. Paoluzzi L, Gonen M, Gardner JR, et al. Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma. Blood 2008;111:5350-8.
48. 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 2006;20:2147-9.
49. Ranger AM, Malynn BA, Korsmeyer SJ. Mouse models of cell death. Nature Genet 2001;28:113-18.
50. Chen L, Willis SN, Wei A, et al. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell 2005;17:393-403.
51. Deng J, Carlson N, Takeyama K, Dal Cin P, Shipp M, Letai A. BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell 2007;12:171-85.
52. van Delft MF, Wei AH, Mason KD, 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 2006;10:389-99.
53. Lin X, Morgan-Lappe S, Huang X, et al. "Seed" analysis of off-target SIRNAS reveals an essential role of Mcl-1 in resistance to the small-molecule Bcl-2/Bcl-xl inhibitor ABT-737. Oncogene 2007;26:3972-9.
54. Tahir SK, Yang X, Anderson MG, et al. Influence of Bcl-2 family members on the cellular response of small-cell lung cancer cell lines to ABT-737. Cancer Res 2007;67:1176-83.
55. Chen S, Dai Y, Harada H, Dent P, Grant S. Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation. Cancer Res 2007;67:782-91.